The national economic burden of cancer: an update.
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Humans↗
Biomedical subjects
M L Brown
Publications and source records attributed to M L Brown.
Increased high-density lipoprotein levels caused by a common cholesteryl-ester transfer protein gene mutation.
BACKGROUND AND METHODS: The plasma cholesteryl-ester transfer protein (CETP) catalyzes the transfer of cholesteryl esters from high-density lipoprotein (HDL) to other lipoproteins. We recently described a Japanese family with increased HDL levels and CETP deficiency due to a splicing defect of the CETP gene. To assess the frequency and phenotype of this condition, we screened 11 additional families with high HDL levels by means of a radioimmunoassay for CETP and DNA analysis. RESULTS: We found the same CETP gene mutation in four families from three different regions of Japan. Analysis of restriction-fragment-length polymorphisms of the mutant CETP allele showed that all probands were homozygous for the identical haplotype. Family members homozygous for CETP deficiency (n = 10) had moderate hypercholesterolemia (mean total cholesterol level [+/- SD], 7.01 +/- 0.83 mmol per liter), markedly increased levels of HDL cholesterol (4.24 +/- 1.01 mmol per liter) and apolipoprotein A-I, and decreased levels of low-density lipoprotein cholesterol (1.99 +/- 0.80 mmol per liter) and apolipoprotein B. Members heterozygous for the deficiency (n = 20), whose CETP levels were in the lower part of the normal range, had moderately increased levels of HDL cholesterol and apolipoprotein A-I and an increased ratio of HDL subclass 2 to HDL subclass 3, as compared with unaffected family members (1.5 +/- 0.8 vs. 0.7 +/- 0.4). CETP deficiency was not found in six unrelated subjects with elevated HDL cholesterol levels who were from different parts of the United States. CONCLUSIONS: CETP deficiency appears to be a frequent cause of increased HDL levels in the population of Japan, possibly because of a founder effect. The results that we observed in heterozygotes suggest that CETP normally plays a part in the regulation of levels of HDL subclass 2. There was no evidence of premature atherosclerosis in the families with CETP deficiency. In fact, the lipoprotein profile of persons with CETP deficiency is potentially antiatherogenic and may be associated with an increased life span.
Adolescent↗
Is the supply of mammography machines outstripping need and demand? An economic analysis.
The number of dedicated mammography machines installed in the United States has grown explosively. It is estimated that almost 10,000 machines will be installed by 1990, whereas the projected demand for screening mammography will require only approximately 2,600 machines, if the machines are used in a moderately efficient manner. The excess supply of mammography resources raises concern from an economic perspective for several reasons. First, such a condition means that health care resources are being used inefficiently. Second, the low average utilization rate of mammography equipment implied by these results necessitates charging a high price-over $100, on average-to cover costs. This price is above the $50 usually associated with low-cost screening mammography programs, and it may impede a desirable public health trend to increase use of mammography screening. Third, the existence of many mammography facilities operating at low capacity levels is inefficient from a health systems perspective, increasing the cost of quality assurance and medical record keeping. The current condition of excess supply is probably unsustainable over the long term.
Costs and Cost Analysis↗
Organization of the human cholesteryl ester transfer protein gene.
The plasma cholesteryl ester transfer protein (CETP) catalyzes the transfer of phospholipids and neutral lipids between the lipoproteins. Thus, this protein may be important in modulating lipoprotein levels in the plasma. We have determined the primary structure and organization of the human CETP gene. Southern blotting of cellular DNA indicated a single copy of the CETP gene exists per haploid genome. Analysis of three overlapping genomic clones showed that the gene spans approximately 25 kbp and contains 16 exons (size range 32-250 bp). Overall, the sequence and organization of the CETP gene do not resemble those of other lipid-metabolizing enzymes or apolipoproteins. However, comparison of the CETP sequence, one exon at a time, with the sequences in the sequence databases revealed a striking identity of a pentapeptide sequence (ValLeuThrLeuAla) within the hydrophobic core of the signal sequences of human CETP, apolipoproteins A-IV and A-I, and lipoprotein lipase. This pentapeptide sequence was not found in the signal sequences of other proteins, suggesting that it may mediate a specialized function related to lipid metabolism or transport.
Amino Acid Sequence↗
Techniques of bone fixation in replantation surgery.
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Bone and Bones↗
Ileocolonic transfer of solid chyme in small intestinal neuropathies and myopathies.
The aims of this study were to assess gastric emptying, small bowel transit and colonic filling in patients with motility disorders, with particular attention to the patterns of colonic filling. Gastrointestinal transit was assessed using a previously validated radiolabeled mixed meal. Fourteen patients with clinical and manometric features of chronic intestinal pseudoobstruction & classified as intestinal neuropathy and 6 as intestinal myopathy, were studied. The results were compared with those from 10 healthy controls studied similarly. Gastric emptying and small bowel transit of solids were significantly slower in both groups of patients than in healthy controls (P less than 0.05). In health, the ileocolonic transit of solid chyme was characterized by intermittent bolus transfers. The mean size of boluses transferred to the colon (expressed as a percentage of ingested radiolabel) was significantly less (P less than 0.05) in patients with intestinal myopathy (10% +/- 4% (SEM)] than in healthy controls (25% +/- 4%) or in patients with intestinal neuropathy (25% +/- 4%). The intervals between bolus transfer of solids (plateaus in the colonic filling curve) were longer (P less than 0.05) in myopathies (212 +/- 89 minutes) than in health (45 +/- 7 minutes) or neuropathies (53 +/- 11 minutes). Thus, gastric emptying and small bowel transit were delayed in small bowel neuropathies and myopathies. Bolus filling of the colon was less frequent and less effective in patients with myopathic intestinal pseudoobstruction, whereas bolus transfer was preserved in patients with neuropathic intestinal pseudoobstruction.
Adult↗
The 'ileal brake' after ileal pouch-anal anastomosis.
The aim of this study was to assess if infusion of oleic acid into the ileal pouch would slow gastric emptying and small-bowel transit, delay defecation, and increase plasma levels of enteroglucagon, neurotensin, or peptide YY in patients with colectomy and ileal pouch-anal anastomosis. Eight subjects with chronic ulcerative colitis who had undergone the operation were studied on 2 consecutive days. On 1 day, saline (154 mM NaCl) was infused into the ileal pouch, and on the other day emulsified oleic acid (152 mM) was infused. The subjects ate a 300-kcal mixed meal containing liquid labelled with 99mTc-DTPA. To assess small-bowel transit concurrently with gastric emptying, a second marker, 111In-DTPA, was instilled through a tube into the duodenum at the end of the meal. Transit of both markers was monitored scintigraphically. Infusion of oleic acid into the ileal pouch slowed gastric emptying and small-bowel transit, and delayed the time to defecation compared with saline infusion. Neither the ileal pouch infusion alone or the meal alone altered plasma levels of enteroglucagon, neurotensin, or peptide YY, but the combination of the oleic acid infusion and the meal increased the levels of all 3 hormones. It was concluded that an "ileal brake" on gastrointestinal transit is functional following ileal pouch-anal anastomosis. Oleic acid placed into the ileal pouch slowed gastrointestinal transit and delayed defecation, effects which may have clinical application. The mechanism mediating the ileal brake may in part be hormonal.
Adult↗
The knowledge and use of screening tests for colorectal and prostate cancer: data from the 1987 National Health Interview Survey.
Data based on the 1987 National Health Interview Survey are presented depicting factors associated with the knowledge and use of three tests for the early detection of colorectal and prostate cancer: digital rectal examination, fecal occult blood tests, and flexible sigmoidoscopy. The percentage of the at risk adult population who have ever heard of or had these tests is reported. The association of demographic, personal resource, and health system factors with knowledge of these tests is explored using multivariate logistic regression. Health system factors are most consistently associated with use of the tests and with knowledge. Family income, family size, education, knowledge of cancer early warning signs, and measures of encounters with the health care system are associated both with knowledge of and, independent of knowledge, with use of the tests. Residency in the non-South, being white or female, and having an optimistic attitude about cancer prevention are all factors associated with greater knowledge of the tests, but not greater use among those aware of the tests. Membership in a health maintenance organization is more strongly associated with knowledge and use of fecal occult blood tests than the other tests. No association was found between current smoking status and knowledge of or use of any of the tests.
Adult↗
Hepatic cyst infection in autosomal dominant polycystic kidney disease.
To characterize the syndrome of hepatic cyst infection in autosomal dominant polycystic kidney disease (ADPKD) and to review its diagnosis and management, we retrospectively studied five such cases in patients from our institution and nine detailed case reports from the literature. The clinical manifestations were an acute (58%) or subacute (42%) febrile illness, typically associated with tenderness in the right upper quadrant, leukocytosis, a very high erythrocyte sedimentation rate, but minor abnormalities of liver function tests. Bacteremia was present in 7 of 11 patients. Enterobacteriaceae grew in pure culture from the cyst fluid in 9 of 12 patients. Complex cysts were observed by ultrasonography (in four of eight patients), computed tomography (in six of nine), and magnetic resonance imaging (in two of two). 111In leukocyte scans were positive in all four patients in whom they were done, and 67Ga scans were positive in only one of three patients. An unfavorable outcome was observed in six of seven patients treated with only antibiotics, in contrast with one of seven patients who received antibiotics and early drainage. In two patients, ciprofloxacin cyst levels were 2.3 and 4.8 times higher than the level in serum; in a third patient, cyst levels remained in therapeutic range 30 hours after the last dose of ciprofloxacin, at which time serum levels were undetectable. Clinical and laboratory features and the use of modern scanning techniques facilitate a prompt diagnosis of infection in hepatic cysts in ADPKD. The treatment of choice is a combination of percutaneous drainage and antimicrobial therapy.
Aged↗
Determination of diastolic function by radionuclide ventriculography.
Diastolic filling can be measured by radionuclide ventriculography with use of several techniques including those based on gated and list-mode acquisitions, the first-pass method, and the nuclear probe. Radionuclide ventriculography specifically assesses volumes, rates of volume change, and intervals during ventricular filling. Normal values for diastolic filling measurement vary depending on the individual radionuclide methods used and the age of the patient. Comparative studies of the radionuclide method with contrast angiographic and Doppler echocardiographic techniques for measuring diastole are discussed, and the advantages and disadvantages of the radionuclide techniques are explored. The role of radionuclide assessment of diastolic function in specific clinical examples of hypertrophic cardiomyopathy, hypertension, anthracycline-induced cardiomyopathy, and coronary artery disease is reviewed. Radionuclide ventriculography is an accurate and easily applicable procedure for studying left ventricular volume changes in diastole.
Aged↗
The presidential effect: the public health response to media coverage about Ronald Reagan's colon cancer episode.
Little previous research has been done on the public health impact of mass media coverage of cancer episodes of public figures. This paper uses a variety of data sources to examine the impact of President Reagan's colon cancer episode of July, 1985. Records of phone calls to the Cancer Information Service of the National Cancer Institute are examined as a measure of public interest and concern about colorectal cancer; data on the use of two colorectal early detection tests--proctoscopy and fecal occult blood tests--are looked at as a measure of behavioral change; and data on the incidence of early and advanced colorectal cancer are used to estimate the potential public health impact of this behavioral change. We find that there was a sharp, albeit somewhat transitory, increase in public interest in colorectal cancer in the wake of President Reagan's colon cancer episode, with a corresponding increase in the use of early detection tests. The incidence data on early and advanced disease is indicative of a beneficial public health impact, but this can be confirmed only after additional data on mortality becomes available.
Attitude to Health↗
Food fights: deciding about diet and disease.
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Diet↗
Effect of captopril on renal function in hypertensive dogs with unilateral renal artery stenosis, studied with radionuclide dynamic scintigraphy.
The kidneys of five hypertensive dogs with experimental unilateral renal artery stenosis were examined by 99mTc-diethylenetriaminepentaacetic acid (DTPA) and 131I-hippuran radionuclide dynamic scintigraphy at 10 and 40 min (respectively) following the administration of intravenous bolus injections of captopril. Doses of 0.2, 0.5, and 1.0 mg/kg captopril reduced mean arterial pressure by 33 +/- 4, 31 +/- 7, and 51 +/- 4 mm Hg and increased plasma renin activity by 40.1 +/- 9.8, 57.6 +/- 3.2, and 34.4 +/- 15.2 ng A1/mL/h, respectively. The time-activity curves of both 99mTc-DTPA and 131I-hippuran indicated that renal excretory function in the stenotic kidney was compromised with all three doses of captopril. However, if nitroprusside was used to reduce the mean arterial pressure to a level comparable to that with captopril, there was no appreciable increase in plasma renin activity and renal excretory function was only partially affected in the stenotic kidney. One hour after the administration of 0.5 mg/kg captopril, the function of the stenotic kidneys was partially restored and, by two hours, the time-activity curves were comparable to control scans. These data demonstrate a reversible, time-limited suppression of stenotic kidney function by captopril in renovascular hypertension and provide support for the use of captopril in the diagnosis of renovascular hypertension by radionuclide dynamic scintigraphy.
Animals↗
Colonic capacitance and transit in man: modulation by luminal contents and drugs.
We have examined whether the human colon is able to adapt its capacity to receive fluid, specifically, whether the caecum and ascending colon ('right colon') exhibited any reservoir function. Healthy volunteers had the caecum intubated from above with a device that permitted intraluminal pressures to be recorded while fluids were instilled into the caecum. Perfusates contained 99mTc-DTPA (diethylenetriamine pentaacetic acid) and volumes of the right colon were determined by two plane scintigraphy using gamma cameras. Different individuals received caecal infusions of 154 mM NaC1 (saline), an emulsion of oleic acid (with bile acids and lecithin) or a 100 mM solution of mixed short chain fatty acids. Each person was pretreated by intravenous saline (placebo), morphine sulphate (100 micrograms/kg) or naloxone (5.5 mg as a bolus, followed by 10 micrograms/kg/min). Volumes of the right colon were smallest during oleic acid infusion; morphine reversed the effect of luminal fat and allowed the colon to accommodate larger volumes. Transit from the right colon was more rapid for the emulsion of oleic acid than it was for saline or solutions of mixed short chain fatty acids. We conclude that the right colon may act as a reservoir and that this function can be modified by the nature of the contents and by pharmacological agents.
Adult↗
Transit of solids through the human colon: regional quantification in the unprepared bowel.
We used a noninvasive method to label the solid phase of contents in the unprepared human colon. 111In-labeled Amberlite pellets (0.5-1.8 mm diam) were placed in a gelatin capsule that was then coated with a pH-sensitive polymer (methacrylate). In vitro, the capsules disintegrated in simulated small bowel contents within 1-2 h; when ingested by healthy subjects, capsules released radiolabel in the distal ileum or proximal colon in 13 of 15 subjects. Transit of 111In-pellets through the unprepared colon could then be quantitated radioscintigraphically. Segmental transit was defined in the ascending (AC), transverse (TC), descending (DC), and rectosigmoid (RS) colon. Radioactivity was also quantitated in stools. At 12 h, radioactivity was most obvious in the AC (59 +/- 11%, mean +/- SE) and the TC (21 +/- 6%); at 24 h, counts were distributed equally between AC, TC, and stools (P greater than 0.05); by 48 h, 56 +/- 11% counts had been excreted, although 30 +/- 10% remained in the TC. At 24 and 48 h, the amount in DC or RS was lower (P less than 0.05) than in the TC or in stools. Emptying of the AC was characterized by an initial lag period, when no counts emptied into the TC, followed by a period of emptying that was approximately linear. Thus this simple approach is able to label contents in the healthy human colon. The ascending and transverse colon appear to be sites of storage of solid residue, whereas the left colon and rectosigmoid function mainly as conduits.
Adult↗
Elevated glucose promotes generation of endothelium-derived vasoconstrictor prostanoids in rabbit aorta.
The effects of glucose on endothelium-dependent responses and vasoactive prostanoid production were determined by incubating isolated rabbit aortae in control (5.5 or 11 mM) or elevated (44 mM) glucose for 6 h to mimic euglycemic and hyperglycemic conditions. Rings of aortae incubated in elevated glucose, contracted submaximally by phenylephrine, showed significantly decreased endothelium-dependent relaxations induced by acetylcholine compared with the aortae incubated in control glucose. Treatment with indomethacin, a cyclooxygenase inhibitor, or SQ29548, a prostaglandin H2/thromboxane A2 receptor antagonist, restored acetylcholine relaxations of rings in elevated glucose to normal, while these agents had no effect on the relaxation of rings incubated in control glucose. Aortae incubated with mannose (44 mM) as a hyperosmotic control relaxed to acetylcholine normally. The relaxations in response to A23187 and sodium nitroprusside were not different between rings exposed to control and elevated glucose. Radioimmunoassay measurements showed a significant increase in acetylcholine-stimulated release of thromboxane A2 and prostaglandin F2 alpha in aortae with, but not without endothelium incubated with elevated, but not with control glucose. Thus a possible mechanism for endothelium dysfunction in diabetes mellitus is the hyperglycemia-induced increased generation of endothelium-derived vasoconstrictor prostanoids.
Acetylcholine↗
Specific effects of ras oncogene expression on the growth and histogenesis of human epidermal keratinocytes.
Little progress has been made in identifying specific regulatory pathways that might be affected in cells by a mutationally activated p21ras when its expression does not lead to complete transformation. We wished to determine whether a normal, diploid human epithelial cell in which activation of ras had occurred could be identified in culture and, furthermore, whether expression of a mutant p21ras in such an otherwise normal cell would result in abnormal histogenic behavior in vivo. Thus, we introduced the v-Ha-ras gene into an early passage culture of normal human epidermal keratinocytes via a defective retrovirus. We examined these genetically engineered cells for changes in growth and differentiation, both in culture and in the epithelium formed when cultures were grafted to the skin of nude mice. We have found that keratinocytes expressing p21v-ras are independent of epidermal growth factor (EGF)--a factor which is normally essential for progressive colony growth, but that they are otherwise indistinguishable in culture from normal cells. v-ras keratinocytes also secrete a factor possessing some specific biological activities of members of the fibroblast growth factor (FGF) family, but which is distinct from acidic and basic FGF. In short-term dermal grafts the v-ras cells form a non-invasive and normally differentiating epidermis. However, the cells express elevated levels of keratin 19, which is a characteristic of fetal epidermis and of premalignant lesions of some stratified squamous epithelia.
Animals↗
The value of indium 111 leukocyte scanning in the evaluation of painful or infected total knee arthroplasties.
Evaluation of painful total knee arthroplasties (TKAs) for infection can be difficult. Indium 111 (111In) leukocyte bone scanning provides a minimally invasive technique for evaluation of possible infection. Thirty-eight patients with a painful TKA who had surgical exploration after 111In leukocyte scanning were reviewed. The scan had an accuracy of 84%, a sensitivity of 83%, and a specificity of 85%. The 111In leukocyte scans must be interpreted in conjunction with the clinical evaluation of the patient because they are less accurate for study of TKAs than of total hip arthroplasties.
Adult↗