Prediction and classification of cardiovascular disease risk in older adults with diabetes.

AIMS/HYPOTHESIS: We sought to derive and validate a cardiovascular disease (CVD) prediction algorithm for older adults with diabetes, and evaluate the incremental benefit of adding novel circulating biomarkers and measures of subclinical atherosclerosis. METHODS: As part of the Cardiovascular Health Study (CHS), a population-based cohort of adults aged ≥65 years, we examined the 10 year risk of myocardial infarction, stroke and cardiovascular death in 782 older adults with diabetes, in whom 265 events occurred. We validated predictive models in 843 adults with diabetes, who were followed for 7 years in a second cohort, the Multi-Ethnic Study of Atherosclerosis (MESA); here 71 events occurred. RESULTS: The best fitting standard model included age, smoking, systolic blood pressure, total and HDL-cholesterol, creatinine and the use of glucose-lowering agents; however, this model had a C statistic of 0.64 and poorly classified risk in men. Novel biomarkers did not improve discrimination or classification. The addition of ankle-brachial index, electrocardiographic left ventricular hypertrophy and internal carotid intima-media thickness modestly improved discrimination (C statistic 0.68; p = 0.002) and classification (net reclassification improvement [NRI] 0.12; p = 0.01), mainly in those remaining free of CVD. Results were qualitatively similar in the MESA, with a change in C statistic from 0.65 to 0.68 and an NRI of 0.09 upon inclusion of subclinical disease measures. CONCLUSIONS/INTERPRETATION: Standard clinical risk factors and novel biomarkers poorly discriminate and classify CVD risk in older adults with diabetes. The inclusion of subclinical atherosclerotic measures modestly improves these features, but to develop more robust risk prediction, a better understanding of the pathophysiology and determinants of CVD in this patient group is needed.

Replication of genetic loci for ages at menarche and menopause in the multi-ethnic Population Architecture using Genomics and Epidemiology (PAGE) study.

STUDY QUESTION: Do genetic associations identified in genome-wide association studies (GWAS) of age at menarche (AM) and age at natural menopause (ANM) replicate in women of diverse race/ancestry from the Population Architecture using Genomics and Epidemiology (PAGE) Study? SUMMARY ANSWER: We replicated GWAS reproductive trait single nucleotide polymorphisms (SNPs) in our European descent population and found that many SNPs were also associated with AM and ANM in populations of diverse ancestry. WHAT IS KNOWN ALREADY: Menarche and menopause mark the reproductive lifespan in women and are important risk factors for chronic diseases including obesity, cardiovascular disease and cancer. Both events are believed to be influenced by environmental and genetic factors, and vary in populations differing by genetic ancestry and geography. Most genetic variants associated with these traits have been identified in GWAS of European-descent populations. STUDY DESIGN, SIZE, DURATION: A total of 42 251 women of diverse ancestry from PAGE were included in cross-sectional analyses of AM and ANM. MATERIALS, SETTING, METHODS: SNPs previously associated with ANM (n = 5 SNPs) and AM (n = 3 SNPs) in GWAS were genotyped in American Indians, African Americans, Asians, European Americans, Hispanics and Native Hawaiians. To test SNP associations with ANM or AM, we used linear regression models stratified by race/ethnicity and PAGE sub-study. Results were then combined in race-specific fixed effect meta-analyses for each outcome. For replication and generalization analyses, significance was defined at P < 0.01 for ANM analyses and P < 0.017 for AM analyses. MAIN RESULTS AND THE ROLE OF CHANCE: We replicated findings for AM SNPs in the LIN28B locus and an intergenic region on 9q31 in European Americans. The LIN28B SNPs (rs314277 and rs314280) were also significantly associated with AM in Asians, but not in other race/ethnicity groups. Linkage disequilibrium (LD) patterns at this locus varied widely among the ancestral groups. With the exception of an intergenic SNP at 13q34, all ANM SNPs replicated in European Americans. Three were significantly associated with ANM in other race/ethnicity populations: rs2153157 (6p24.2/SYCP2L), rs365132 (5q35/UIMC1) and rs16991615 (20p12.3/MCM8). While rs1172822 (19q13/BRSK1) was not significant in the populations of non-European descent, effect sizes showed similar trends. LIMITATIONS, REASONS FOR CAUTION: Lack of association for the GWAS SNPs in the non-European American groups may be due to differences in locus LD patterns between these groups and the European-descent populations included in the GWAS discovery studies; and in some cases, lower power may also contribute to non-significant findings. WIDER IMPLICATIONS OF THE FINDINGS: The discovery of genetic variants associated with the reproductive traits provides an important opportunity to elucidate the biological mechanisms involved with normal variation and disorders of menarche and menopause. In this study we replicated most, but not all reported SNPs in European descent populations and examined the epidemiologic architecture of these early reported variants, describing their generalizability and effect size across differing ancestral populations. Such data will be increasingly important for prioritizing GWAS SNPs for follow-up in fine-mapping and resequencing studies, as well as in translational research.

Soluble intracellular adhesion molecule-1 is associated with cardiovascular disease risk and mortality in older adults.

BACKGROUND: Intracellular adhesion molecule-1 (ICAM-1) regulates leukocyte-endothelial attachment, a process crucial to atherosclerosis. Circulating soluble ICAM-1 (sICAM-1) may serve as a marker of cardiovascular disease (CVD) progression. OBJECTIVES: We examined the association of sICAM-1 with measures of subclinical CVD and risk of incident CVD events and death in older men and women (age > or = 65 years) from the Cardiovascular Health Study. METHODS: Selected participants were free of clinical CVD at baseline. Non-exclusive incident case groups were angina (n = 534), myocardial infarction (n = 304), stroke (n = 327), and death (n = 842; CVD death = 310). A total 643 subjects were free of events during follow-up. RESULTS: sICAM-1 was positively associated with C-reactive protein, interleukin-6 and fibrinogen and measures of subclinical CVD in these older men and women. In Cox regression models adjusted for age, gender, and race, increasing levels of sICAM-1 were associated with increased risk of all cause mortality in men and women. Hazard ratios (95% confidence intervals) for a one standard deviation increase in sICAM-1 (89.7 ng mL(-1)) were 1.3 (1.1-1.4) in men and 1.2 (1.1-1.3) in women. sICAM-1 was associated with increased risk of CVD death in women (1.2; 1.0-1.5), but not men (1.1; 0.9-1.3). There were no associations of sICAM-1 with non-fatal CVD events. CONCLUSIONS: While sICAM-1 was associated with death in older men and women, there was a more marked association between sICAM-1 and CVD death in women.

Chemotherapy can prolong survival in patients with advanced non-small-cell lung cancer--report of a Canadian multicenter randomized trial.

The survival benefit of combination chemotherapy to patients with advanced non-small-cell carcinoma of the lung (NSCLC) is controversial. To study this question, the National Cancer Institute of Canada (NCIC) Clinical Trials Group conducted a prospective randomized trial comparing best supportive care (BSC) to two chemotherapy regimens, vindesine and cisplatin (VP), and cyclophosphamide, doxorubicin, and cisplatin (CAP). Between February 1983 and January 1986, 23 centers across Canada entered 251 patients on study. Eighteen centers participated in the three-arm schema (150 patients); centers choosing not to participate in a study with a no-chemotherapy arm followed a two-arm schema comparing VP with CAP (101 additional patients). Altogether, 233 patients were eligible. Patients had measurable or evaluable disease, with either distant metastases (82.5%) or bulky limited disease considered inoperable or unsuitable for radical radiotherapy. The treatment groups were comparable in terms of age, sex, performance status, histology, disease extent, and weight loss. The overall response rates (complete response [CR] plus partial response [PR]) on the chemotherapy arms were CAP, 15.3%, and VP, 25.3% (P = .06). Patients on the three-arm portion of the trial had a median survival of 32.6 weeks when treated with VP, 24.7 weeks with CAP, and 17 weeks with BSC. The significance of the differences in survival, adjusted for prognostic factors, is as follows: chemotherapy v BSC, P = .02; VP v BSC, P = .01; and CAP v BSC, P = .05. Toxicity on the chemotherapy arms was significant, with leukopenia of severe or greater degree occurring in 37.8% (CAP) and 40.0% (VP), severe vomiting in 12.2% (CAP) and 23.3% (VP), and severe neurotoxicity in 15.6% (VP).

Risk stratification for long-term outcome after elective coronary angioplasty: a multivariate analysis of 5,000 patients.

OBJECTIVES: We attempted to develop a statistical model to facilitate risk stratification for long-term outcome after elective coronary angioplasty. BACKGROUND: Our understanding of factors related to long-term outcome after coronary angioplasty is limited. Adequate assessment of risk indexes could potentially lead to more appropriate use of percutaneous revascularization. METHODS: We studied 5,000 consecutive patients and assessed 19 clinical and anatomic variables as predictors of long-term event-free survival. Events were defined as death of any cause, myocardial infarction, bypass surgery or repeat percutaneous transluminal coronary angioplasty. Cox proportional hazards models were used to develop an equation for predicting event-free survival in a subset of 4,000 patients. The equation was validated with the remaining 1,000 patients. Variables that were significantly associated with an adverse outcome in the multivariate model included age > 60 years, extent of disease, Canadian Cardiovascular Society functional class, previous coronary angioplasty, male gender, history of diabetes mellitus, history of hypertension and history of congestive heart failure. RESULTS: The statistical model was used to develop a simplified scoring system, and the patients were assigned to three risk subgroups. Event-free survival curves for the three groups were significantly different (p = 0.0001). High risk patients had worse outcomes for each of the end points compared with low and moderate risk patients (p < 0.02). CONCLUSIONS: We demonstrated that clinical and anatomic variables can be used to risk-stratify long-term outcome after angioplasty, that a simplified scoring system can be used for risk stratification and that high risk patients have a low event-free survival.

Predictors of congestive heart failure in the elderly: the Cardiovascular Health Study.

OBJECTIVES: We sought to characterize the predictors of incident congestive heart failure (CHF), as determined by central adjudication, in a community-based elderly population. BACKGROUND: The elderly constitute a growing proportion of patients admitted to the hospital with CHF, and CHF is a leading source of morbidity and mortality in this group. Elderly patients differ from younger individuals diagnosed with CHF in terms of biologic characteristics. METHODS: We analyzed data from the Cardiovascular Health Study, a prospective population-based study of 5,888 elderly people >65 years old (average 73 +/- 5, range 65 to 100) at four locations. Multiple laboratory measures of cardiovascular structure and function, blood chemistries and functional assessments were obtained. RESULTS: During an average follow-up of 5.5 years (median 6.3), 597 participants developed incident CHF (rate 19.3/1,000 person-years). The incidence of CHF increased progressively across age groups and was greater in men than in women. On multivariate analysis, other independent predictors included prevalent coronary heart disease, stroke or transient ischemic attack at baseline, diabetes, systolic blood pressure (BP), forced expiratory volume 1 s, creatinine >1.4 mg/dl, C-reactive protein, ankle-arm index <0.9, atrial fibrillation, electrocardiographic (ECG) left ventricular (LV) mass, ECG ST-T segment abnormality, internal carotid artery wall thickness and decreased LV systolic function. Population-attributable risk, determined from predictors of risk and prevalence, was relatively high for prevalent coronary heart disease (13.1%), systolic BP > or =140 mm Hg (12.8%) and a high level of C-reactive protein (9.7%), but was low for subnormal LV function (4.1%) and atrial fibrillation (2.2%). CONCLUSIONS: The incidence of CHF is high in the elderly and is related mainly to age, gender, clinical and subclinical coronary heart disease, systolic BP and inflammation. Despite the high relative risk of subnormal systolic LV function and atrial fibrillation, the actual population risk of these for CHF is small because of their relatively low prevalence in community-dwelling elderly people.

Lack of association of the plasminogen activator inhibitor-1 4G/5G promoter polymorphism with cardiovascular disease in the elderly.

Elevated circulating plasminogen activator inhibitor-1 (PAI-1) may increase risk of cardiovascular disease (CVD). The 4G allele of the 4G/5G PAI-1 promoter polymorphism is associated with higher levels of PAI-1. We examined the association of PAI-1 4G/5G genotype and CVD events in the elderly participants of the Cardiovascular Health Study (CHS). We measured 4G/5G genotype in a nested case-control study within the CHS. Cases included incident angina, myocardial infarction (MI), and stroke. 4G/5G genotype was not found to be associated with markers of fibrinolysis or CVD risk in the selected elderly cohort. There were no differences in genotype frequencies by case-control status (5G/5G frequency 16-22%; chi2P= 0.07). The 5G allele was not associated with incident CVD events when individuals with at least one 5G allele were compared to 4G/4G homozygotes. The presence of at least one 4G allele was likewise not associated with incident CVD when those with 4G/4G and 4G/5G genotypes were compared to 5G/5G homozygotes. Our results suggest that the PAI-1 4G/5G promoter polymorphism is not associated CVD risk factors or incident CVD events in the elderly.

Gender differences for coronary angioplasty.

To determine if differences in early and late outcome after angioplasty were related to gender or body surface area, 5,000 consecutive patients (1,274 women and 3,726 men) were studied. Baseline variables, procedural outcome, and long-term and event-free survival were assessed. Baseline variables included age, history of hypertension, diabetes mellitus, heart failure, myocardial infarction, prior angioplasty or bypass surgery, familial coronary disease, Canadian heart classification, extent of angioplasty, left ventricular function, and body surface area. Overall and event-free survival (freedom from infarction, repeat angioplasty, bypass surgery and death) were assessed at follow-up. The results showed that, compared with men, women were older (p < 0.0001), had a higher prevalence of diabetes (p < 0.0001), familial coronary disease (p = 0.002), hypertension (p < 0.0001), prior infarction (p = 0.004), and more involvement of the anterior descending artery (p = 0.017). Whereas men had similar extents of angioplasty and worse left ventricular function (p = 0.012), women more often had unstable angina (p < 0.0001). The success rates were similar, yet women had a higher procedural mortality (1.1% women, 0.3% men, p = 0.001). When corrected for body surface area, however, women were at no greater risk than men. Follow-up was complete for 97.4% of patients (mean 4 +/- 2 years). Event-free survival was significantly better in women, even after correcting for body surface area. Men were at higher risk for late death and repeat angioplasty on follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Ultrasound imaging of the radial artery following its use for cardiac catheterization.

Our experience suggests transradial arterial access with 5Fr catheters can be used for cardiac angiography with a low incidence of clinical complications, and supports the findings of previous investigators. Subclinical complications at the catheterization site were infrequent in this study (1 patient with asymptomatic radial artery occlusion). The presence of a palpable radial pulse may not be a reliable estimate of artery patency as evidenced by our patient with a palpable pulse due to retrograde flow. The theoretical advantage of the procedure is derived from the dual vascular supply to the hand. Radial artery occlusion, while uncommon, results in no ischemic sequelae in the setting of a patent ulnar artery.

Left ventricular diastolic filling in the elderly: the cardiovascular health study.

Changes in left ventricular (LV) diastolic function (e.g., as measured by transmitral flow velocity) are known to occur with aging. In addition, impaired LV diastolic function plays an important role in such cardiovascular disorders common in the elderly as hypertension, ischemic heart disease, and congestive heart failure (CHF). Participants in the Cardiovascular Health Study, a multicenter study of community-dwelling men (n=2,239) and women (n=2,962) > or = 65 years of age, underwent an extensive baseline evaluation, including echocardiography. Early diastolic LV Doppler (transmitral) peak filling velocity decreased, and peak late diastolic (atrial) velocity increased with age in multivariate analyses (all p <0.001). Early and late diastolic peak filling velocities were both significantly higher in women than in men, even after adjustment for body surface area (or height and weight). In multivariate models in the entire cohort and a healthy subgroup (n=703), gender, age, heart rate, and blood pressure (BP) were most strongly related to early and late diastolic transmitral peak velocities. Early and late diastolic peak velocities both increased with increases in systolic BP and decreased with increases in diastolic BP (p <0.001). Doppler transmitral velocities were compared among health status subgroups. In multiple regression models adjusted for other covariates, and in analysis of variance models examining differences across subgroups adjusted only for age, the subgroup with CHF had the highest early diastolic peak velocities. All clinical disease subgroups had higher late diastolic peak velocities than the healthy subgroup, with the subgroups with either CHF or hypertension having the highest age-adjusted means. The subgroup with hypertension had the lowest ratio of early-to-late diastolic peak velocity, and men with CHF had the highest ratio. These findings are consistent with previous reports that hypertensive subjects exhibit an abnormal relaxation pattern, whereas patients with CHF develop a pattern suggestive of an increased early diastolic left atrial-LV pressure gradient.

Ontogeny of growth hormone, insulin-like growth factor-I, estradiol and cortisol in the growing lamb: effect of testosterone.

Exogenous sex steroids have altered growth hormone secretion in some domestic species. This study examined whether different physiological concentrations of testosterone alter muscle growth in sheep through modification of the somatotropic axis. The effects of testosterone on growth hormone (GH), insulin-like growth factor-I (IGF-I), estradiol (E2) and cortisol concentrations in growing lambs were evaluated in 20 rams, 20 wethers and 20 wethers receiving subcutaneous testosterone replacement therapy. Two animals from each of the three testosterone status groups were slaughtered at 14-day intervals from 49 to 133 days of age, and then at 28-day intervals until 217 days of age for a total of 10 slaughter ages. Animals were sampled every 10 min for an 8-h period 1 day prior to slaughter to characterize the episodic patterns of GH and testosterone. Immediately after slaughter, the semitendinosus, splenius and triceps brachii muscles were removed, trimmed of adhering fat and connective tissue, and weighed. Testosterone increased the combined muscle weight. GH concentrations decreased during the course of the experiment. However, there was no effect of testosterone on GH mean, baseline, amplitude or GH pulse frequency measured by PULSAR. IGF-I concentrations increased in response to testosterone treatment. Testosterone had no effect on cortisol levels while E2 levels were increased after 133 days. Increased muscle growth due to testosterone appeared to be caused either by a direct effect or by increased levels of IGF-I independent of circulating GH concentrations.

Factors associated with healthy aging: the cardiovascular health study.

OBJECTIVES: To identify factors associated with remaining healthy in older adults. DESIGN: Longitudinal cohort study. SETTING: Data were collected at the four Cardiovascular Health Study field centers. PARTICIPANTS: 5,888 participants age 65 years and older in the Cardiovascular Health Study. MEASUREMENTS: Presence of chronic disease was assessed at baseline and over a maximum 7-year follow-up period. Participants who were free of chronic disease (no cardiovascular disease (CVD), chronic obstructive pulmonary disease, or self-reported cancer, except nonmelanoma skin cancer) at the baseline examination were then monitored for the onset of incident cancer, cardiovascular disease, and fatal outcomes. RESULTS: A high proportion of these older adults was healthy at the initial examination and remained healthy over the follow-up period. Numerous behavioral factors were associated with continued health, including physical activity, refraining from cigarette smoking, wine consumption (women), higher educational status, and lower waist circumference. A number of CVD risk factors and subclinical disease measures were associated with continued health, including higher high-density lipoprotein (HDL) cholesterol, lack of diabetes, thinner common carotid intimal nmedial thickness, lower blood pressure, lower C-reactive protein, and higher ankle-arm blood pressure ratio. Among the behavioral factors, exercise, not smoking, and not taking aspirin remained significant predictors of health even after controlling for CVD risk factors and subclinical disease in older adults. CONCLUSIONS: These data suggest that a number of modifiable behavioral factors (physical activity, smoking, and obesity) and cardiovascular risk factors (diabetes, HDL cholesterol, and blood pressure) are associated with maintenance of good health in older adults.

Inhibition of radiation cataractogenesis by WR-77913.

The radioprotective drug S-3-amino-2-hydroxypropylphosphorothioic acid (WR-77913) has been tested as an inhibitor of radiation cataractogenesis. Animals treated with 15 Gy whole-head 137Cs gamma radiation developed mature cataracts 10-12 weeks after irradiation. Intraperitoneal pretreatment with 815 mg/kg WR-77913 30 min before irradiation delayed the development of cataracts; mature cataracts required 42 weeks for development. Doses as low as 350 mg/kg, substantially below the toxic range, resulted in graded but incomplete protection and a significant delay in the development of cataracts. Drug treatment combined with radiation doses of 12.5 or 10 Gy showed less pronounced protection. The optimum time of drug delivery was found to be between 30 min and 2 h before irradiation; protective action diminished if longer times were used or if the drug was given after irradiation. These results are discussed in relation to those obtained with other chemical radioprotective agents and in terms of possible mechanisms of the action of the drug.

Podophyllotoxin derivative VP 16-213.

VP 16-213, a derivative of podophyllotoxin, is currently entering phase-III studies. Its mode of action is incompletely understood, but differs markedly from that of its parent compound. The greatest lethal damage is experienced by cells in the late S and G2 phases. In the L 1210 system the drug shows marked schedule dependency: prolonged administration may be more effective than single bolus administration. As a single agent, VP 16-213 is the most active compound yet tested against small-cell bronchial carcinoma. It may also prove to be a useful agent in patients with other types of lung tumour, testicular teratomas, and some types of leukaemia. No long-term or cumulative toxicity has been reported. Most side effects are predictable and reproducible.

Measurement of water sorption by resin composite adhesives with near-infrared spectroscopy.

Spectroscopic methodology was used to follow the water uptake of disks of two resin composite luting agents during long-term storage. Fourier-transform near-infrared (FT-NIR) spectroscopy was used for collection of spectra over the 4200-6500 cm-1 spectral region. The 5200-cm-1 absorption band of water was monitored initially, at 24 h, seven days, two weeks, and then monthly over a period of 12 months. The disks were stored in water, air, and desiccated conditions. Disks were also subjected to two alternate cycles (two weeks each) of hydration and desiccation. A spectral manipulation program was used for quantitation of the area under the water absorbance band. Area ratios demonstrated similar water-uptake patterns for the two adhesives. Rapid water uptake was seen within the first two weeks of storage. Alternate hydration and desiccation of the samples showed that water uptake by the filler/polymer network was partially reversible. The desiccant was unable to remove all the water from the samples, which indicated that some water was tightly held within the sample matrix. FT-NIR spectroscopy is recommended as an effective method for study of the equilibration of resin composites in water.

Tensile fatigue limits of prosthodontic adhesives.

Tensile fatigue limits and ultimate tensile strengths of some prosthodontic adhesive systems were determined. Ni-Cr-Be cylinders were: electro-etched, chemically etched, and sand-blasted prior to being bonded end-to-end with BIS-GMA and 4-META adhesives. Bonded specimens were stored in distilled de-ionized water for three days prior to being tested. Fifteen paired specimens per group were subjected to a cyclic tensile load for 1000 cycles. Tensile fatigue limits were determined by the staircase method. Five specimens per group were tested for ultimate tensile strength. In addition, those specimens which survived the 1000 cycles during fatigue testing were also tested for ultimate tensile strength. Statistical evaluations to compare tensile fatigue limits and ultimate tensile strengths for fatigued and non-fatigued specimens were then performed. The results indicated that the tensile fatigue limit and the ratio of fatigue limit to ultimate tensile strength of the sand-blasted, 4-META adhesive system were significantly lower than those of the other systems tested. The application of a cyclic load significantly decreased the ultimate tensile bond strength of the 4-META adhesive. Application of a cyclic load had no significant effect on the ultimate tensile bond strengths of the BIS-GMA systems tested.

Analysis of debond rates of resin-bonded prostheses.

Debonding rates of 164 resin-bonded prostheses (RBP) placed from 1974 to 1985 were examined at recall. The yearly debond rates were calculated, the cumulative probability of failure was determined for the debonded RBPs, and Weibull distribution parameters were determined. For perforated prostheses, there was a high initial debond rate, followed by slowly decreasing rates for about 5 years. Increasing rates after 5 years indicated the beginning of wear-out. The Weibull parameters for the wear-out period of the perforated prostheses were: characteristic life = 128 (SE = 2) months, modulus = 1.27 (0.06), and threshold parameter = 0. Data were available for etched frameworks for 6 years and showed decreasing debond rates during this time. The characteristic life of the etched bridges was 318 (84) months. The cumulative failure data were also modeled with a cubic polynomial distribution that resulted in a U-shaped hazard function.

Photocoagulation treatment for clinically significant radiation macular oedema.

Macular oedema is a leading cause of vision loss in patients with radiation retinopathy. In an effort to find an effective treatment for this vision threatening complication, 12 eyes (eight patients) were treated with photocoagulation for clinically significant radiation macular oedema (CSRMO) defined as central macular thickening, exudates threatening the macular centre, or one disc area of thickening in the macula. Median visual acuity improved from 20/100 preoperatively to 20/90 at the initial postoperative examination (mean follow up 5 months) and to 20/75 at the final postoperative examination (mean follow up 39 months). At the final postoperative examination, visual acuity had improved in eight (67%) eyes and six (50%) eyes had complete resolution of the CSRMO; two (17%) other eyes had improved anatomically in that fewer CSRMO criteria were present. These results suggest that macular photocoagulation is effective in decreasing macular oedema and improving vision in eyes with CSRMO.

Optical detection of pulpal blood.

An optical system to assess blood within the pulpal cavity was developed. The system included a light-emitting diode source, human incisor teeth, and a silicon photodiode detector. An automated syringe pump was used to flow bovine blood lengthwise through the teeth. Transmitted light intensities were recorded at a collection frequency of 20 reading/min and apparent absorbance units were calculated. The effects of blood concentration, blood flow rate, and pulp chamber size were investigated. It was found that changes in blood flow rate did not cause significant changes in transmitted light intensity. Increases in blood concentration and pulp chamber size resulted in larger absorbance values. These results suggest that photoplethysmography measurements may be sensitive to the amount of blood in the pulp chamber as it reflects the pulsatile-related expansion and contraction of capillaries within the pulp tissue.

Optical detection of hemoglobin in pulpal blood.

An in vitro, flow-through optical system was designed to measure hemoglobin (Hb) concentrations in the pulp space. The system included light-emitting diodes and a silicon photodetector positioned on opposing surfaces of human teeth. A syringe pump allowed a controlled flow of blood through the pulp chamber. The Hb concentration was computed as a nonlinear function of transmitted light intensity. Transmitted light intensities were also used as indicators of oxygenation level. Optical measurements correlated with Hb values measured by the conventional cyanmethemoglobin method (r=0.993). The mean percentage error was 5.8%, and the standard error of prediction was 0.77 g/dl for Hb concentrations ranging from 4 to 20 g/dl. Deoxygenated blood exhibited up to 31% lower transmitted intensity. Light transmission through teeth may be useful in the assessment of total Hb and blood oxygenation within the pulp chamber.