1. Possible defects in cholesterol metabolism were sought in children with familial hypercholesterolaemia. 2. In nine affected children (eight heterozygotes and one homozygote) and in five healthy children, cholesterol synthesis and bile acid synthesis were determined from the excretion of steroids in the faeces during a low cholesterol diet. Cholesterol synthesis of 10.1 f 4.4 mg day-’ kg-I in the hypercholesterolaemic children was similar to that in these and other normal children. Mean bile acid synthesis of 4.0 f 2.1 mg day-l kg-l also resembled normal values though three severely affected heterozygotes excreted substantially less. 3. The response to 4 weeks’ additional 450 mg of dietary cholesterol/day led to variable changes in the plasma cholesterol and in the sterol balance. On average the affected children showed a rise in plasma cholesterol which resembled that in healthy subjects. The sterol balance fell in most, suggesting a reduction in cholesterol synthesis, which is the normal response to dietary cholesterol. 4. The response to dietary cholesterol was therefore at least qualitatively similar in the hypercholesterolaemic children to that reported in healthy subjects.

Background Elevated lipoprotein(a) [Lp(a)] levels have been associated with the presence of atherosclerotic disease. However, the results of prospective studies of Lp(a) and cardiovascular disease have been contradictory.Methods and Results From 1968 through 1982, lipoprotein analysis was performed in 11 335 Olmsted County residents. Quantitative cholesterol and triglycerides were obtained along with semiquantitative Lp(a) levels based on electrophoretic pattern. Lp(a) bands were scored from 0 (absent) to 3 (increased). A cohort of 4967 men and 4968 women with no prior history of atherosclerotic disease who had baseline Lp(a) determinations were followed up for 14 years for development of coronary artery disease (CAD) and cerebrovascular disease (CVD). During 131 330 person-years of follow-up, there were 1848 CAD events and 841 CVD events. Age, diabetes, hypertension, cholesterol, and triglycerides were significantly and independently associated with an increased risk of CAD and CVD in men and women. There was a significant increase in the adjusted hazards ratio for CAD with increasing Lp(a) levels for men and women. For Lp(a) level 3, the hazard ratio was 1.9 (range, 1.3 to 2.9) in women and 1.6 (range, 1.0 to 2.5) in men. The adjusted hazard ratio for CVD showed an irregular association with Lp(a) levels in men and no association in women.Conclusions In this cohort of 9936 men and women initially free of cardiovascular disease who were followed up for 14 years, LP(a) was a significant-predictor of risk of future CAD. Lp(a) was a weak risk factor for CVD in men and was not a significant predictor of CVD risk in women.

Background: Blood products like hemoglobin are problematic as markers for colorectal neoplasia because bleeding is intermittent. Levels of calprotectin, a leukocyte-derived protein, are increased in stools from colorectal cancer patients. However, this blood constituent may gain luminal access via interstitial leukocyte migration, which could be a less variable mechanism of entry than bleeding. Methods: To correlate the levels of and to compare the variability of fecal calprotectin and hemoglobin, quantitative assays were performed independently on multiple serially collected stools from 14 patients with colorectal cancer. Marker level association was estimated with Pearson's correlation coefficient, and variation estimated with an analysis of variance model. Results. Fecal calprotectin and hemoglobin levels were discordant in 55 (50%) of 110 matched aliquots, and marker levels failed to correlate. The estimated between-subject correlation was -0.10 (95% CI, -0.60 to 0.46), and mean within-subject correlation -0.27 (95% CI, -0.73 to 0.34). The between-stool coefficient of variation was less for calprotectin (22%) than for hemoglobin (80%). Conclusions: In patients with colorectal cancer, the mechanism of luminal calprotectin entry appears to be both different from and less erratic than bleeding.

Objectives.-To define the validity of fecal blood as a marker for colorectal neoplasia in the screening setting and to compare yields by Hemoccult and HemoQuant fecal occult blood screening tests.Design.-A multicenter masked comparison of fecal blood test results against structural colorectal evaluations and longitudinal follow-up, serving as criterion standards, in nonreferred subjects at risk for colorectal neoplasia.Setting.-Communities, primary care centers, referral centers.Participants.-Two groups: (1) 1217 patients aged at least 18 years undergoing routine structural surveillance evaluations following curative resection of a colorectal tumor and (2) 12312 relatives of colorectal cancer patients aged at least 50 years.Interventions.-Blinded Hemoccult II and HemoQuant testing on three mailed-in stool samples per subject.Main Outcome Measure.-Sensitivity of fecal blood tests for colorectal neoplasia.Results.-In the postresection group, surveillance evaluations revealed 46 malignant colorectal neoplasms and 402 polyps. At matched specificity, sensitivity of either test for cancer was 26% (95% confidence interval, 13% to 39%). Hemoccult was positive in 21% of intraluminal recurrences, 33% of all new primary tumors, and 29% of Dukes A or B cancers; HemoQuant was elevated in 24%, 28%, and 29%, respectively. Sensitivity for polyps 1.0 cm or larger was 13% by Hemoccult and 11 % by HemoQuant. In the group of relatives, estimated sensitivity for cancer at 1 to 3 years of follow-up was 25% to 33% by Hemoccult, not significantly different from the 29% to 43% by HemoQuant.Conclusions.-Based on our observations in the screening setting, fecal blood appears to be a poor marker for colorectal neoplasia. Most cancers and the vast majority of polyps will be missed. Hemoccult and HemoQuant are similarly insensitive.

In 36 normolipemic pigs randomized to a 4-week feeding with regular pig chow (n = 18, control group) or chow supplemented with cod liver oil (1 ml/kg per day) (n = 18, treated group), treatment with cod liver oil produced a significant decrease in serum cholesterol, low density lipoprotein cholesterol, and triglycerides. Deep carotid arterial wall injury (media exposed) by balloon angioplasty was associated with less 111In-labeled platelet deposition (24.6 +/- 4.8 x 10(6)/cm2 versus 62.5 +/- 17.0 x 10(6)/cm2, p less than 0.05; difference, -33.8 x 10(6)/cm2; 95% confidence interval [CI], -1.9 x 10(6)/cm2 to -73.9 x 10(6)/cm2) and injury-related vasoconstriction (21.3 +/- 2.2% versus 30.9 +/- 2.9%, p less than 0.05; difference, -9.6%; 95% CI, -2.2% to -17.0%) in the cod liver oil-treated group than in the control group; with mild injury (media not exposed), platelet deposition was low and unchanged (6.2 +/- 0.5 x 10(6)/cm2 versus 7.8 +/- 0.7 x 10(6)/cm2; difference, -1.6 x 10(6)/cm2; 95% CI, -1.1 x 10(6)/cm2 to +4.3 x 10(6)/cm2), but associated vasoconstriction was reduced respectively (16.3 +/- 2.0% versus 23.0 +/- 2.2%, p less than 0.05; difference, -6.7%; 95% CI, -0.6% to -12.8%). When arterial blood from cod liver oil-treated pigs superfused normal aortic media ex vivo, platelet deposition onto the normal aortic media was lower than when arterial blood from control pigs superfused the normal aortic media (43.7 +/- 8.8 x 10(6)/cm2 versus 66.8 +/- 13.0 x 10(6)/cm2, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Hemoglobin-heme is variably converted to porphyrin during enterocolic transit. This intestinal converted fraction, as measured by HemoQuant, was elevated as a predictor of the occult bleeding site in 152 patients with discrete lesions. The intestinal converted fraction, expressed as the percentage of total fecal hemoglobin, was similar with upper gastrointestinal and proximal colon lesions. Within the colon, values trended downward with more distal location: means ± standard deviations were 18±14 proximal colon, 16 ±15 sigmoid, and 10±10 rectum. The amount of fecal blood also affected the intestinal converted fraction; correcting for hemoglobin concentration improved separation by site. Corrected intestinal converted fraction values were significantly lower with rectal (P< 0.0005) and sigmoid (P<0.02) lesions than with proximal colon lesions. Unfortunately, large within-site variation caused considerable overlap between sites. We conclude that the intestinal converted fraction is influenced by the site and amount of bleeding. However, its clinical utility is compromised by substantial individual differences in luminal hemoglobin metabolism.

We have purified Lp(a) lipoproteins from sera of four subjects by ultracentrifugation, selective precipitation, and chromatofocusing. Each subject had two forms of serum Lp(a) that were separable by chromatofocusing. We purified apolipoprotein (a) [apo(a)] from the eight isolated Lp(a)s and obtained only one form of apo(a) from each subject. The four apo(a)s seen on sodium dodecyl sulfate-polyacrylamide gel electrophoresis had different apparent molecular masses, ranging from 275 to 440 kDa. Chemical deglycosylation of the smallest apo(a) yielded a 235 kDa protein, which may be a core protein structure common to all apo(a)s. We conclude that there are many forms of serum Lp(a) and apo(a). The heterogeneity of serum Lp(a) particles can be ascribed in part to differences in size of apo(a), but other factors must account for the existence within a single patient of different Lp(a)s that contain apparently identical apo(a). One must consider the heterogeneity of Lp(a) when designing assays for this lipoprotein.

We sought to determine the short-term effects of use of aspirin and ethanol on fecal occult blood levels measured with the HemoQuant assay. A factorial design was used to study 68 healthy volunteers randomized to receive various doses of aspirin, ethanol, or a combination of both for either 1 or 3 days. Fecal hemoglobin concentrations were measured before and after drug ingestions. Moderate quantities of ethanol (300 ml of 5% or 30 ml of 50% three times nightly) did not cause significant fecal blood elevation unless aspirin was administered concomitantly (P = 0.05). High-dose aspirin alone, 975 mg three times daily, induced abnormal blood loss (P less than 0.01). The highest HemoQuant levels were usually noted after concomitant administration of aspirin and ethanol at maximal doses for 3 days (P less than 0.005), some HemoQuant levels approaching 5 times the normal value. We conclude that, in a short-term analysis, social consumption of ethanol is unlikely to interfere with fecal blood testing but therapeutic doses of aspirin will.

Unfortunately, Mr. Holmes never divulged the principle of his infallible procedure. Despite the contempt of Holmes for the “old guaiacum test… very clumsy and uncertain,” physicians have continued to rely on guaiac and related tests for the detection of blood. Now from another century and another continent, Dr. Samuel Schwartz, the colleague of another Dr. Watson (Dr. Cecil Watson), has developed the HemoQuant * HemoQuant assay, United States patent no. 4,378,971, now owned by American Bio-Science Laboratories. *HemoQuant assay, United States patent no. 4,378,971, now owned by American Bio-Science Laboratories. assay for fecal blood. 1 Schwartz S Dahl J Ellefson M Ahlquist D The “HemoQuant” test: a specific and quantitative determination of heme (hemoglobin) in feces and other materials. Clin Chem. 1983; 29: 2061-2067 Crossref PubMed Scopus (117) Google Scholar Like the test of the legendary supersleuth, HemoQuant measures “haemoglobin and…nothing else” with high sensitivity “whether the blood is old or new.” It is intriguing that the fluorescence of heme-derived porphyrins, the basis of the HemoQuant assay, is a beautiful deep red. Thus this new test is truly “a study in scarlet,” although not in quite the same sense as in Sir Arthur Conan Doyle's classic tale of revenge that first introduced to the world the redoubtable duo of Sherlock Holmes and Dr. Watson.

Seventy-two amniocenteses with concurrent placental grading by ultrasound were performed during 66 pregnancies. No relationship was observed between placental grade and the mean ratio of lecithin to sphingomyelin (L/S) or the phosphatidylglycerol concentration. Both placental grade and fetal lung maturity were interrelated by the independent variable of gestational age. The latter may explain the trend observed between a mature L/S ratio and the placental grade. Grade 3 placentas were present in only 20% of patients studied at 37 weeks of gestation or later (12 of 61 patients), and in every instance a Grade 3 placenta was associated with an absence of neonatal respiratory distress.