A piece of my mind. A simple act.
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Child↗
Biomedical subjects
R Green
Publications and source records attributed to R Green.
Reduction of beta-amyloid peptide42 in the cerebrospinal fluid of patients with Alzheimer's disease.
In this clinical study the cerebrospinal fluid (CSF) level of a novel form of the beta-amyloid peptide (A beta) extending to position 42 (A beta 42) was determined in patients with Alzheimer's disease (AD) as well as controls. In addition to measurement of CSF A beta 42 levels, total A beta peptides, microtubule-associated protein tau, and apolipoprotein E (ApoE) genotype were also assessed. It is interesting that CSF A beta 42 levels were found to be significantly lower in AD patients relative to controls, whereas total A beta levels were not. A beta 42 has recently been shown to preferentially deposit in the brain tissue of patients with AD, suggesting that diminished clearance may account for its reduction in CSF. As previously reported, tau levels were increased in AD patients; however, neither A beta 42 nor tau levels were apparently influenced by the ApoE genotype.
Aged↗
Linkage analysis of 26 Canadian breast and breast-ovarian cancer families.
We have examined 26 Canadian families with hereditary breast or ovarian cancer for linkage to markers flanking the BRCA1 gene on chromosome 17q12-q21. Of the 15 families that contain cases of ovarian cancer, 94% were estimated to be linked to BRCA1. In contrast, there was no overall evidence of linkage in the group of 10 families with breast cancer without ovarian cancer. A genetic recombinant in a breast-ovarian cancer family indicates a placement of BRCA1 telomeric to D17S776, and helps to define the region of assignment of the cancer susceptibility gene. Other cancers of interest that appeared in the BRCA1-linked families included primary peritoneal cancer, cancer of the fallopian tube, and malignant melanoma.
Adult↗
Do Australian women have greater spinal bone density than North American women?
The interpretation of bone mineral densitometry results for a particular individual relies on valid reference data from a representative population sample. To establish local reference data, 411 Australian female volunteers had bone mineral densitometry performed at a single medical centre at the proximal femur and lumbar spine using a Hologic QDR 1000-W dual-energy X-ray absorptiometer. These data were compared with reference material from North American women compiled by Hologic. The Australian volunteers had, on average, 7% greater bone mineral density at the lumbar spine for the age range 25-55 years. Possible explanations for this include an actual population difference or the presence of a differential selection bias between the two samples.
Adolescent↗
Metabolic correlates of neurologic and behavioral injury after prolonged hypothermic circulatory arrest.
Thirty-two inbred weanling puppies were divided into four groups to study the effect on cerebral blood flow and metabolism of different hypothermic strategies for cerebral protection similar to those used during cardiac operations in infancy. All animals were cooled to 18 degrees C. The animals in the hypothermic control group were immediately rewarmed. One group underwent 30 minutes of hypothermic circulatory arrest at 18 degrees C; another group had 90 minutes of hypothermic circulatory arrest at 18 degrees C, and the final group had low-flow cardiopulmonary bypass (25 ml/kg per minute) at 18 degrees C for 90 minutes. All animals had preoperative and postoperative neurologic and behavioral evaluation and extensive intraoperative monitoring of cerebral blood flow, cerebral vascular resistance, and oxygen and glucose uptake and metabolism: quantitative electroencephalography was also monitored before, during and after operation, but those results are reported separately. Two animals in the 90-minute arrest group died, and all the survivors showed evidence of clinical, neurologic, and behavioral impairment on postoperative day 1, with residual abnormalities in all but one animal on day 6. In contrast, the survivors in all the other groups showed no significant clinical or behavioral sequelae. Cerebral metabolism was reduced only to 32% to 40% of baseline values at 18 degrees C in all groups, although systemic metabolism was only 16% of normal. Cerebral metabolism returned promptly to baseline in all groups during rewarming and remained at baseline levels throughout the 8 hours of follow-up. Cerebral blood flow showed marked hyperemia in the hypothermic arrest groups during rewarming but then significant reductions below baseline values in all groups except the controls at 2 and 4 hours after the operation, lasting as late as 8 hours after the operation in the 90-minute arrest group. Cerebral vascular resistance showed increases in all groups at 2 and 4 hours after the operation, which persisted in the 90-minute arrest group at 8 hours. Cerebral metabolism was maintained at baseline levels despite postoperative decreases in cerebral blood flow and increases in cerebral vascular resistance by increases in oxygen and glucose extraction. The result was very low sagittal sinus oxygen saturations in all groups, most marked in the 90-minute arrest groups, which had a saturation of only 24% 8 hours after the operation. Our data show a severe, prolonged disturbance in cerebral blood flow and cerebral vascular resistance after 90 minutes of hypothermic circulatory arrest at 18 degrees C, which correlates with clinical evidence of cerebral injury.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Metabolite assays in cobalamin and folate deficiency.
Cbl and folate are both necessary for the metabolism of HCYS, whereas only Cbl is required for MMA metabolism. During the past decade, analytical methods have been developed that are sensitive enough to detect low levels of MMA and HCYS normally present in the plasma. These methods are sufficiently precise to be used in the clinical laboratory and measurements of the serum levels of the metabolites provide sensitive and specific techniques for the identification of Cbl and folate deficiencies. These techniques constitute an important addition to the battery of diagnostic tests that are available for detecting the vitamin deficiencies and for distinguishing each from the other. By virtue of the role of Cbl and folate in the metabolic pathways that involve MMA and HCYS, levels of both metabolites rise in Cbl deficiency, but only HCYS rises in folate deficiency. During the development of Cbl or folate deficiencies, accumulation of these metabolites in the plasma signals the existence of a condition of biochemical vitamin deficiency of sufficient degree to cause impairment in the metabolic pathways which are dependent on these vitamins. Circulating metabolite levels appear to accurately reflect the nutritional status of the vitamins and a rise in serum metabolite levels is therefore one of the earliest and most reliable indicators of developing Cbl and folate deficiencies. Elevations of serum metabolites above the reference range not only precede a fall in the serum vitamin levels but also show a more consistent correlation with objective evidence of vitamin deficiency than do low blood vitamin levels. The advent of serum metabolite measurements has also made it possible to identify subtle or atypical forms of vitamin deficiency that may be associated with unusual or previously undiscovered disease manifestations. Thus, in patients who display only neurological manifestations of disease, underlying Cbl deficiency may be revealed by the finding of raised serum or urine levels of MMA. Similarly, unsuspected folate deficiency may be disclosed by the finding of a raised serum HCYS. This may have important implications with respect to disease risk, since there is mounting evidence that sub-optimal folate nutritional status may be associated with increased risks of vascular disease, neoplasia and birth defects. Finally, the measurement of serum levels of MMA, HCYS and other metabolites that accumulate in Cbl and folate deficiencies may provide important new insights into the mechanism whereby these vitamin deficiencies lead to different patterns and manifestations of disease.
Folic Acid Deficiency↗
The frequently low cobalamin levels in dementia usually signify treatable metabolic, neurologic and electrophysiologic abnormalities.
Cobalamin levels are frequently low in patients with dementia, but it is unclear if they represent definable deficiency and what the mechanisms are. Therefore, patients being evaluated for dementia who had low cobalamin levels but no obvious evidence of deficiency were studied hematologically, neurologically and with metabolic tests and were re-evaluated after cobalamin treatment. Abnormalities suggestive of or diagnostic for deficiency were documented in most of the 16 demented and nondemented patients. Metabolic results: 50% of patients tested had abnormal deoxyuridine suppression and 44% had increased serum methylmalonic acid and/or homocysteine levels; these test results correlated with each other. Neurologic results: 73% of patients had clinical abnormalities, primarily mild neuropathies, not attributable to other causes, 75% had electroencephalographic abnormalities, 77% had abnormal visual evoked potentials and 33% had abnormal somatosensory potentials. Metabolic and neurologic dysfunction were present together or absent together in all but 2 cases. Cobalamin therapy improved 50-100% of the various types of abnormalities, although it did not improve cognitive function in the 13 demented patients. Food-cobalamin malabsorption was found in 60% of the patients. Despite the absence of megaloblastic anemia and rarity of traditional malabsorption of free cobalamin, low cobalamin levels in demented patients frequently represent mild cobalamin deficiency and are often associated with food-cobalamin malabsorption. Perhaps most importantly, this is accompanied not only by metabolic changes but by evidence of mild neurologic dysfunction. Their frequent reversibility by cobalamin confirms that these defects indeed arise from cobalamin deficiency. Although the long-standing dementia does not improve, treating such patients with cobalamin has other concrete benefits.
Aged↗
Effect of barium on potassium diffusion across the proximal convoluted tubule of the anesthetized rat.
The role of diffusion in transepithelial potassium flux and the importance of potassium channels in the luminal cell membrane to this process were examined by applying a luminal microperfusion technique to surface tubules in kidneys of anesthetized rats. Potassium concentration gradients were applied by altering the concentration of KCl in perfusates. To some perfusates, 2 mmol/l BaCl2 was added to block potassium channels in the luminal cell membrane. The mean applied potassium concentration gradient was highly predictive of net potassium transport in the absence of any change in fluid reabsorption, with an apparent potassium permeability of 22 x 10(-5) cm/s. Thus potassium transport in the proximal tubule may have an important diffusive component. Luminal barium significantly reduced the concentration of potassium in collected fluid under conditions of net potassium secretion, although a substantial barium-insensitive potassium permeability was also observed. However, the site of action of luminally applied barium is uncertain in proximal tubule, since barium was reabsorbed by the tubule at a rate of 13.6 pmol.mm-1.min-1. We conclude that diffusion is a significant driving force for potassium reabsorption in proximal tubule and that most diffusive potassium transport occurs via a barium-insensitive route, possibly the paracellular pathway.
Animals↗
A major histocompatibility complex class I-related Fc receptor for IgG on rat hepatocytes.
Intestinal epithelial cells of the neonatal rat and mouse have been shown to express a major histocompatibility complex (MHC) class I-like Fc receptor, or FcRn, which transports IgG in an apical to basolateral direction. Previous studies have suggested the possible expression of this receptor beyond the neonatal period within the liver. Since bile contains high levels of IgG, we sought to determine whether the FcRn was functionally expressed by adult rat hepatocytes. Using primers specific for FcRn, which did not cross hybridize with MHC class I transcripts, FcRn DNA was amplified by reverse transcriptase polymerase chain reaction from RNA of adult rat hepatocytes. This RNA contained functional FcRn transcripts as it encoded a beta 2-microglobulin-associated cell surface protein as determined by immunoprecipitation of biotinylated cell surface proteins with a polyclonal anti-FcRn specific antiserum. Western blotting of hepatocyte canalicular (apical) and sinusoidal (basolateral) plasma membranes with an FcRn-specific monoclonal antibody further confirmed the protein expression and suggested that FcRn was enriched on the canalicular surface membranes. FcRn, on the surface of hepatocytes, was biologically functional as it bound Fc fragments of IgG at pH 6.0 but not 8.0, which is the same pH dependence observed for FcRn in rat neonatal enterocytes. Thus, FcRn is functionally expressed outside of the neonatal period on the canalicular cell surface of adult hepatocytes. This suggests that hepatocyte FcRn may bind luminal IgG, providing a potential functional communication between parenchymal immune cells and bile.
Animals↗
Current concepts in the diagnosis of cobalamin deficiency.
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Humans↗
'Anesthesia paresthetica': nitrous oxide-induced cobalamin deficiency.
A man with a subclinical cobalamin deficiency developed syncope, vertigo, paresthesias, and ataxia after two exposures to nitrous oxide anesthesia. Patients with unrecognized cobalamin deficiency may be particularly susceptible to brief exposures to nitrous oxide, which inactivates the cobalamin-dependent enzyme methionine synthase and may cause a myeloneuropathy. Clinicians should consider this entity when confronted with patients with neuropathic symptoms after surgical or dental procedures.
Aged↗
Measuring productivity in health care.
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Australia↗
A rare breed.
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American Medical Association↗
Leaders in medicine: Robert K. Endres MD.
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History, 20th Century↗
Comparison of a generic (SF-36) and a disease specific (WOMAC) (Western Ontario and McMaster Universities Osteoarthritis Index) instrument in the measurement of outcomes after knee replacement surgery.
OBJECTIVE: The discriminant validity of a generic, health related quality of life (HRQL) measure, the SF-36, was compared with that of a disease specific HRQL measure, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), in patients aged 67-99 years who had undergone knee replacement surgery 2 to 7 years previously. METHODS: A stratified random sample of 1750 Medicare beneficiaries was surveyed and 1193 usable responses were obtained (after adjustment for ineligible, incapacitated, and deceased individuals). Discriminant validity of scale scores common to both instruments (pain, physical functioning, and overall score) were compared. RESULTS: Examination of discriminant validity, using Spearman correlations, showed that the WOMAC discriminates better among individuals with knee problems, while the SF-36 discriminates better among individuals with varying levels of self reported general health status and comorbidities. CONCLUSION: These scales measure 2 distinct but important aspects of patients' health. These results support inclusion of both a generic and a disease specific HRQL measure in cross sectional studies.
Aged↗
Comparison of a generic and a disease-specific measure of pain and physical function after knee replacement surgery.
Generic and disease-specific health status instruments are commonly used to assess patients' outcomes. The hypothesis that they measure distinct but complementary aspects of patients' quality of life was tested using a sample of patients aged 67 to 99 years who had undergone knee replacement surgery 2 to 7 years previously. Patients' scores on a generic health-related quality-of-life (HRQOL) measure, the SF-36, were compared to those of the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index; the WOMAC was developed specifically for patients with lower extremity arthritis, whereas the SF-36 is aimed at all conditions. A stratified sample of 1,750 Medicare beneficiaries was surveyed and an overall response rate of 80.3% achieved, resulting in 1,193 usable surveys (after adjustment for ineligible, incapacitated, and deceased individuals). The distribution of scores on the three dimensions common to both instruments (i.e., pain, physical function, and overall score) showed consistently higher scores on the WOMAC, on a scale of 0 (worst) to 100 (best), than on the SF-36, indicating less disability from arthritis than from other conditions after knee surgery in this elderly population. Statistically significant differences in the number of people with perfectly healthy scores were detected between the instruments; with regard to pain, 32.2% of the sample reported no pain due to arthritis on the WOMAC, compared with only 13.6% reporting no pain due to any conditions on the SF-36. The figures for physical function and overall score were 9.6% versus 1.4%, and 6.9% versus 0.2%, respectively. Examination for discriminant validity showed that the scores on the two scales followed hypothesized patterns: the WOMAC discriminated better among subjects with varying severity of knee problems, whereas the SF-36 discriminated better among subjects with varying levels of self-reported health status and comorbidity. The results of this study support the inclusion of both a generic and a disease-specific HRQOL measure to assess patient outcomes fully.
Aged↗
Clearer images in pediatric MRI.
Pediatric outpatient magnetic resonance imaging (MRI) was a frustrating experience for both patients and staff at London, Ontario's University Hospital until nurses, the child-life specialist, physicians and technicians got together and developed the Pediatric MRI Sedation Program.
Adolescent↗
Joan K. Leavitt, MD. The commish moves on.
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History, 20th Century↗