Consensus Conference on Nasal Polyposis.
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Biomedical subjects
Publications and source records attributed to G M Halpern.
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Diet and fatty acid metabolism interact in yet unknown ways to modulate membrane fatty acid composition and certain cellular functions. For example, dietary precursors or metabolic products of n-3 fatty acid metabolism differ in their ability to modify specific membrane components. In the present study, the effect of dietary 22:6n-3 or its metabolic precursor, 18:3n-3, on the selective accumulation of 22:6n-3 by heart was investigated. The mass and fatty acid compositions of individual phospholipids (PL) in heart and liver were quantified in mice fed either 22:6n-3 (from crocodile oil) or 18:3n-3 (from soybean oil) for 13 wk. This study was conducted to determine if the selective accumulation of 22:6n-3 in heart was due to the incorporation of 22:6n-3 into cardiolipin (CL), a PL most prevalent in heart and known to accumulate 22:6n-3. Although heart was significantly enriched with 22:6n-3 relative to liver, the accumulation of 22:6n-3 by CL in heart could not quantitatively account for this difference. CL from heart did accumulate 22:6n-3, but only in mice fed preformed 22:6n-3. Diets rich in non-22:6n-3 fatty acids result in a fatty acid composition of phosphatidylcholine (PC) in heart that is unusually enriched with 22:6n-3. In this study, the mass of PC in heart was positively correlated with the enrichment of 22:6n-3 into PC. The increased mass of PC was coincident with a decrease in the mass of phosphatidylethanolamine, suggesting that 22:6n-3 induced PC synthesis by increasing phosphatidylethanolamine-N-methyltransferase activity in the heart.
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A lipid-rich extract, prepared by supercritical fluid (CO2) extraction of freeze-dried stabilized NZ green-lipped mussel powder (Lyprinol) has shown significant anti-inflammatory (AI) activity when given to animals and humans. When treated p.o. with Lyprinol, Wistar and Dark Agouti rats developed neither adjuvant-induced polyarthritis or collagen(II)-induced auto-allergic arthritis. This was achieved with doses < NSAIDs, and 200 times < of other seed or fish oils. Lyprinol subfractions inhibited LTB4 biosynthesis by PMN in vitro, and PGE2 production by activated macrophages. Much of this AI activity was associated with omega-3 PUFAs and natural antioxidants [e.g. carotenoids]. In contrast to NSAIDs, Lyprinol is non-gastro toxic in disease-stressed rats at 300 mg/kg p.o., and does not affect platelet aggregation [human, rat]. Clinical studies, either controlled or randomized, have demonstrated very significant AI activity in patients with osteoarthritis (OA), rheumatoid arthritis (RA), asthma, and other inflammatory conditions. Lyprinol is a reproducible, stable source of bioactive lipids with much greater potency than plant/marine oils currently used as nutritional supplements to ameliorate signs of inflammation.
This review presents Cordyceps sinensis (Berk.) Sacc., a fungus highly valued in China as a tonic food and herbal medicine. The extant records show the continued use of C. sinensis is now centuries old. The major chemical, pharmacological, and toxicological studies on C. sinensis and the various derived, cultured, fermented mycelial products currently in use are reviewed from the English and Chinese literature. Preclinical in vitro and in vivo studies and clinical blinded or open-label trials in to date over 2000 patients are reviewed. These studies show the main activities of the fungus in oxygen-free radical scavenging, antisenescence, endocrine, hypolipidemic, antiatherosclerotic, and sexual function-restorative activities. The safety of the fungus, its effects on the nervous system, glucose metabolism, the respiratory, hepatic, cardiovascular, and immune systems, immunologic disease, inflammatory conditions, cancer, and diseases of the kidney will be reviewed in the second part of this article to be published in the winter issue of this journal.
Cordyceps sinensis (Berk.) Sacc. is a time-honored tonic food and herbal medicine in China, where recent research has shown that many of its traditional uses may be viewed from the basis of pharmacological activities. The ongoing exploration of C. sinensis in its wild form and cultured, fermented mycelial products derived from it, are reviewed from English and Chinese literature. Part II concludes the series with a review of C. sinensis in preclinical in vitro and in vivo studies, and open-label and double-blinded clinical trials on the respiratory, renal, hepatic, cardiovascular, immunologic, and nervous systems, and its effects on cancer, glucose metabolism, inflammatory conditions, and toxicological studies. In Part I, which appeared in the Fall 1998 issue of this journal (4(3):289-303), we discussed the effects of C. sinensis on antisenescence, endocrine and sexual functions, atherosclerosis, hyperlipidemia, and free radicals.
The metabolic fate of silicone gel leaked into the body from an implant is unknown. In this study, serum from 72 women with silicone gel breast implants and 55 control women was blindly assayed by inductively coupled plasma atomic emission spectroscopy (ICP-AES) for elemental silicon. Samples were processed using materials free of silicon. The mean silicon level in controls was 0.13 +/- 0.07 mg/l (range 0.06-0.35 mg/l), while in implant patients, the mean was significantly higher at 0.28 +/- 0.22 mg/l (range 0.06-0.87 mg/l) (P < 0.01, Student's t-test with correction for unequal variances). Using the mean of the control group + 2 SD as a cutoff for normal range (0.27 mg/l), 25/72 (34.7%) implant patients exceeded this value, compared with 2/55 (3.6%) controls. There was no significant correlation between past rupture of one or both implants, current rupture at the time of the blood draw or the number of years with implants and silicon levels. The results suggest that elevations of serum silicon are seen in many women with silicone gel breast implants. The kinetics of this elevation and the actual chemical species of the measured silicon remain to be determined.
OBJECTIVE: To assess the efficacy of Lacteol Fort, an antidiarrheal drug, in patients suffering from the chronic intestinal disease known as irritable bowel syndrome (IBS). DESIGN: The randomized, double-blind, cross-over trial versus placebo was carried out from 1992 to 1994. This trial consisted of administering a 6-wk treatment with a first drug (Lacteol Fort or placebo), followed by a wash-out period of 2 wk, and then the administration of a second drug for a further 6 wk (placebo or Lacteol Fort). Among the 29 patients eligible after recruitment, 18 adults with well documented IBS fulfilled the inclusion criteria. Four patients were dropped for loss of materials used in the study and seven for lack of compliance. The patient's initial state was assessed using a questionnaire relating to six criteria: abdominal pain, bloating or gas, daily number of stools, consistency, mucus content, and general physical state. During the treatment, these criteria were evaluated daily by the patients themselves. RESULTS: All investigated criteria were scored, and then a daily mean index was calculated. The statistical analysis of the daily mean index values showed that the number of patients (nine cases) obtaining better results with Lacteol Fort than with placebo was statistically significant (p = 0.018). CONCLUSIONS: This double-blind, placebo-controlled, cross-over trial demonstrated that Lacteol Fort leads to a statistically significant therapeutic benefit in 50% of patients, when taking into consideration all of the six selected clinical criteria considered representative of IBS.
The metabolic fate of silicone gel leaked from an intact or ruptured prosthesis is unknown. In this study, serum was blindly assayed by inductively coupled plasma atomic emission spectroscopy (ICP-AES) for elemental silicon in 72 women with silicone gel breast implants and 55 control women (mean age 48 yr, both groups). Blood was drawn and processed using silicon-free materials. The mean silicon level in controls was 0.13 +/- 0.07 mg/L (range 0.06-0.35 mg/L), whereas in implant patients, the mean was significantly higher at 0.28 +/- 0.22 mg/L (range 0.06-0.87 mg/L) (P < 0.01, Student's t-test with correction for unequal variances). Using the mean of the control group + 2 SD as a cutoff for normal range (0.27 mg/L), 25/72 (34.7%) implant patients exceeded this value, compared with 2/55 (3.6%) controls. There was no significant correlation between past rupture of one or both implants, current rupture at the time of the blood draw, or the number of years with implants and silicon levels. The results suggest that serum silicon levels are elevated in many women with silicone gel breast implants. The chemical species involved and kinetics of this elevation remain to be determined.
The sick building syndrome has been widely discussed from epidemiological perspectives. Although there is considerable difference in opinion regarding the concrete and objective evidence to support a distinct sick building syndrome and/or building-related illness, much data indicates that numerous variables within buildings can potentially influence human health. In this paper, we discuss in detail not only the potential and unique infectious diseases caused by Legionella, Pontiac fever, Q fever, and influenza, but also the data implicating noninfectious etiologies of sick building syndrome and building-related illnesses. In addition, the role of psychological factors, mass hysteria, and indoor pollution is discussed with respect to the nature of associations between exposure and symptoms. Finally, comparisons are made in different building construction types of old versus new buildings to highlight changes in modern construction that may have led to a putative increase in work-related symptomatology.
OBJECTIVE: To test the effect of substituting a modified-fat cheese product into the diets of hypercholesterolemic adults. DESIGN: A 4-month, randomized, double-blind, crossover substitution trial. SETTING: General community outpatient study. PARTICIPANTS: Twenty-six healthy adult volunteers (17 men, 9 women) with moderate hypercholesterolemia (total cholesterol > 5.69 mmol/L but < 7.24 mmol/L). INTERVENTION: Daily substitution of 100 g of cheese, either partial skim-milk mozzarella or modified-fat (vegetable oil) mozzarella cheese product, into participants' normal diets. Participants consumed an assigned cheese for 2 months, at which time they crossed over to consume the other study cheese. MAIN OUTCOME MEASURES: Plasma lipid and apolipoprotein levels were measured at baseline and at 2 and 4 months after initiation of the study. Compliance was assessed by body weight and by biweekly dietary records and interviews. RESULTS: No differences in weight or in the amount or type of calories consumed were found during the study. No statistically significant changes in lipid values resulted from consumption of mozzarella cheese. Modified-fat cheese substitution resulted in a decreased low-density lipoprotein cholesterol level when compared with levels at both baseline (-0.28 mmol/L; 95% Cl, -0.14 to -0.42 mmol/L) and during consumption of the skim-milk mozzarella cheese (-0.38 mmol/L; 95% Cl, -0.2 to -0.70 mmol/L). Findings for total cholesterol were similar. High-density lipoprotein cholesterol, plasma triglyceride, and apolipoprotein A-l and B-100 levels were unaltered. Both sexes responded similarly. CONCLUSIONS: A linoleate-enriched cheese product, in the absence of any other changes in diet or habits, substituted into the normal diets of hypercholesterolemic adults reduced low-density lipoprotein and plasma cholesterol levels.
There is a general consensus that the mortality rates for asthma in much of the developed world have been increasing for the past 10-15 years. This has occurred despite an improved information base regarding diagnosis and management as well as the development of novel and more effective therapeutic modalities. Several explanations have been proposed for this increase, including a statistical artifact based on a change in the coding criteria for asthma from the International Classification of Diseases Version 8 (ICD-8) to ICD-9, worsened pollution, delays in seeking medical help, behavioral changes, deficits in asthma education of both patients and primary care providers, toxicity of beta agonists, and noncompliance with medications. We suggest that although all of these are potential etiological factors, there may exist still another major etiological risk. There have been dramatic changes in our eating habits and food preparation. In general, we eat less total calories, more meals outside the home, and more refined or prepared foods. With the emphasis on reducing the intake of saturated fats and cholesterol, we eat more polyunsaturated fats both by choice and secondary to manufacturers' attempts to improve the appeal of foods to health-conscious government and the public. The drive to remove animal fats and cholesterol from our diet has resulted in the replacement of animal fats with vegetable oil in food manufacture, fast-food frying, and even home preparation. One result of these dietary habits has been a doubling from 8 to 15% of the percentage of the polyunsaturated linoleic acid in body fat. We postulate that this, and other nutritional changes, will render asthma a more difficult syndrome to manage and will contribute adversely to the inflammatory abnormalities in airways.
It has been difficult to confirm that a given building is responsible for allergic symptomatology, exacerbation of asthma, or immunological dysfunction. In fact, in most studies, few objective immunological parameters have been studied and only rarely has there been any quantitation of IgE or secondary mediators. Furthermore, although many studies deal with rhinitis or respiratory tract irritation, there is a misconception that all such symptoms are allergic in nature, and studies attempting to prove that allergies are caused by buildings frequently neglect to prove that these are indeed true allergic responses. In addition, many of the symptoms that people attribute to sick building syndrome (SBS) or building-related illness, such as headaches, dizziness, fatigue, nausea, cough, and eye irritation, are subjective, and studies often fail to take into account other possible causes that may be inherent in the subjects, such as sinusitis, hyperventilation syndrome, or psychosomatic illness. Unfortunately, most clinical studies on SBS pay little attention to the preexisting conditions that a subject may have and discount the possibility that the inciting agent does not cause symptoms, but merely exacerbates a preexisting condition. Moreover, they offer no information about the nature of the mechanisms of action or pathophysiological relationships. Clearly, further studies are necessary to further explain the complexity of complaints that currently exist. Indeed, SBS might properly be paraphrased as "what is it?--if it is!"
Indoor air pollution is closely associated with health problems and exacerbation of asthmatic symptoms. However, it is difficult to find objective data regarding the nature of these illnesses and the degree of exposure necessary to elicit symptoms in building occupants. Clinicians must be encouraged to take seriously, and without bias, workers' complaints about their work environment. However, this is often a problem because of subjective complaints, potential malingerers, mass hysteria, and lack of impartial clinical and laboratory findings. Clearly, in any building, a major priority must be to provide and maintain an environment conducive to occupant health and well-being. Allowable levels of air pollutants must be scientifically determined by health investigators based on government regulations. Unfortunately, regulations are often ill defined, unenforceable, and burdened by a void as to who is responsible for achieving a healthful indoor environment. The elucidation of the multiple causes of illnesses secondary to indoor air pollution can be addressed by greater attention to design, construction, and operation of buildings where people live and work. Finally and most important, the federal government should bear the responsibility for funding the necessary research to solve the nation's indoor air quality problems.
The HRT Assay was evaluated for its capacity to measure histamine release from blood basophils following the introduction of extracts from catheters made of Aquavene or silicone. Blood samples were collected from twenty-one volunteers of the University of California, Davis campus and from seven individual who had experienced a systemic event during the insertion of catheters made from Aquavene. None of the blood samples released histamine in quantities that would be anticipated in an anaphylactic or anaphylactoid reaction when challenged with the extracts; all released histamine when challenged with polymyxin B, used as a positive control. Based upon these results, none of the components of either the Aquavene-based or silicone-based catheters are thought to cause a histamine-associated reaction in subjects. This assay proved to be both expedient and reliable in its determination of the release of histamine from blood basophils.
Forty-nine sera from patients with food allergies confirmed by challenge and of 14 with suspected allergy were assayed with the DPC AlaSTAT liquid phase EIA and the Phadebas RAST CAP radioimmunoassay (RIA). Twenty-two foods were tested (four animals, 18 vegetables). Controls were performed on nonatopic subjects (N = 8). Specificity was 100%. Concordance RAST CAP/AlaSTAT was 79.6%; prick tests/AlaSTAT: 76%; prick tests/RAST CAP: 73.9%. AlaSTAT detected specific IgE even in sera with low total IgE (< 60 KU/L), while RAST CAP was inconclusive. Dilution studies and reproducibility were excellent. AlaSTAT EIA compares favorably with the Phadebas RAST CAP RIA for measurement of food-specific IgE antibodies.
Human IgG subclasses play a major role in the physiological regulation and functions of the immune system. There "personality" is obvious. However, the determination requires appropriate reagents and technology. For the IgG1, IgG2, IgG3 subclasses, the radial immunodiffusion technique may be sufficient. For the IgG4 subclass determination and measurement, more elaborate techniques are required. These measurements of existing proteins are of major interest in congenital as well as acquired immune deficiencies more often, besides the total subclass deficiency, these are of utmost interest to evaluate the specific response of a given subclass to a specific antigen. The IgG4 allergen specific subclass has been considered to be involved both in allergic reactions and associated with the appropriate response to allergen-specific immunotherapy. It is now accepted that IgG4 does not play an discernable role in the acute inflammatory response of type I hypersensitivity; it has also been demonstrated that a number of patients who demonstrate elevated levels of allergens specific IgG4 are not protected against allergenic exposure, and conversely, a number of patients who have been heated by immunotherapy without demonstrating any significant increase in their serum levels of allergen specific IgG4 are indeed very well protected. In the field of allergy, the IgG4 determinations remain a matter of controversy and research.
Mast cells contain proteoglycans, e.g. heparin, which manifest potent anti-inflammatory features. Mast cell degranulation could eventually result in self limiting inflammation with shortened course due to heparin release. The recent availability of low molecular weight heparins will allow for clinical studies in allergic/inflammatory syndromes, e.g. asthma.