Journal of Nutritional & Environmental Medicine

Published by Informa Healthcare
Online ISSN: 1364-6907
Publications
Human neuronal (nNOS), endothelial (eNOS) and inducible nitric oxide synthase (iNOS) domain structure (PDZ domain, named after homologous domains in three proteins: PSD-95, DH/g, ZO-1).
Model of nitric oxide synthase oxygenase (NOSox) dimer with approximate scheme for hypothetical glutathionylcobalamin (GSCbl) links in relation to the two hemes, ZnS4, BH4, arginine. Ser 104 is in the loop with the Cys ligands and H bonds to the C6 side chain of BH4.
Article
Several mysteries surround the structure and function of the nitric oxide synthases (NOS). The NOS oxygenase domain structure is unusually open with a large area of solvent that could accommodate an unidentified ligand. The exact mechanism of the two-step five-electron monoxygenation of arginine to N(G)-hydroxy-L-arginine, thence to citrulline and nitric oxide (NO), is not clear, particularly as arginine/N(G)-hydroxy-L-arginine is bound at a great distance to the supposed catalytic heme Fe [III], as the anti-stereoisomer. The Return of the Scarlet Pimpernel Paper proposed that cobalamin is a primary indirect regulator of the NOS. An additional direct regulatory effect of the 'base-off' dimethylbenzimidazole of glutathionylcobalamin (GSCbl), which may act as a sixth ligand to the heme iron, promote Co-oriented, BH(4)/BH(3) radical catalysed oxidation of L-arginine to NO, and possibly regulate the rate of inducible NOS/NO production by the NOS dimers, is further advanced. The absence of homology between the NOS and methionine synthase/methylmalonyl CoA mutase may enable GSCbl to regulate both sets of enzymes simultaneously by completely separate mechanisms. Thus, cobalamin may exert central control over both pro-and anti-inflammatory systems.
 
Structure of vitamin B12 and its derivatives.
‘What goes around comes around’: some central cobalamin relationships.
Human neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS) domain structure. The PDZ domain is named after homologous domains in three proteins: PSD-95, DH/g, ZO-1.
Structure of 6R-5,6,7,8-tetrahydro-L-biopterin (BH4), the naturally occurring pterin cofactor of nitric oxide synthases and amino acid hydroxylases. The standard nomenclature for numbering the positions of the pteridine ring and the biopterin side chain is indicated.
Article
The up-regulation of transcobalamins [hitherto posited as indicating a central need for cobalamin (Cbl) in inflammation], whose expression, like inducible nitric oxide synthase (iNOS), is Sp1- and interferondependent, together with increased intracellular formation of glutathionylcobalamin (GSCbl), adenosylcobalamin (AdoCbl), methylcobalamin (MeCbl), may be essential for the timely promotion and later selective inhibition of iNOS and concordant regulation of endothelial and neuronal NOS (eNOS/nNOS.) Cbl may ensure controlled high output of nitric oxide (NO) and its safe deployment, because: (1) Cbl is ultimately responsible for the synthesis or availability of the NOS substrates and cofactors heme, arginine, BH(4) flavin adenine dinucleotide/flavin mononucleotide (FAD/FMN) and NADPH, via the far-reaching effects of the two Cbl coenzymes, methionine synthase (MS) and methylmalonyl CoA mutase (MCoAM) in, or on, the folate, glutathione, tricarboxylic acid (TCA) and urea cycles, oxidative phosphorylation, glycolysis and the pentose phosphate pathway. Deficiency of any of theNOS substrates and cofactors results in 'uncoupled' NOS reactions, decreasedNO production and increased or excessive O(2) (-), H(2)O(2), ONOO(-) and other reactive oxygen species (ROS), reactive nitric oxide species (RNIS) leading to pathology. (2) Cbl is also the overlooked ultimate determinant of positive glutathione status, which favours the formation of more benign NO species, s-nitrosothiols, the predominant form in which NO is safely deployed. Cbl status may consequently act as a 'back-up disc' that ensures the active status of antioxidant systems, as well as reversing and modulating the effects of nitrosylation in cell signal transduction.New evidence shows that GSCbl can significantly promote iNOS/ eNOS NO synthesis in the early stages of inflammation, thus lowering high levels of tumour necrosis factor-a that normally result in pathology, while existing evidence shows that in extreme nitrosative and oxidative stress, GSCbl can regenerate the activity of enzymes important for eventual resolution, such as glucose 6 phosphate dehydrogenase, which ensures NADPH supply, lactate dehydrogenase, and more; with human clinical case studies of OHCbl for cyanide poisoning, suggesting Cbl may regenerate aconitase and cytochrome c oxidase in the TCA cycle and oxidative phosphorylation. Thus, Cbl may simultaneously promote a strong inflammatory response and the means to resolve it.
 
Article
PIP A child responds to a deficiency of an essential nutrient either by continuing to grow and consuming body stores with eventual reduction in the bodily functions (Type I) or by reducing growth and avidly conserving the nutrient to maintain the concentration of the nutrient in the tissues (Type II). Examples of Type I nutrient deficiency are anemia (iron deficiency), beri-beri (thiamin deficiency), pellagra (niacin or nicotinic acid deficiency), scurvy (vitamin C or ascorbic acid deficiency), xerophthalmia (vitamin A or retinol deficiency) and iodine deficiency disorders. Diagnosis is relatively simple via clinical symptoms and measurement of the concentration of the nutrient itself. There are no characteristic symptoms to distinguish which Type II nutrient deficiency an individual has; all deficiencies result in the poor growth, stunting, and wasting generally ascribed to protein-energy malnutrition. In Type II, growth stops, the body starts to conserve the nutrient, and its excretion falls to very low levels. In severe deficiency the body may start to break down its own tissues and the reduction of appetite accompanies this condition. An animal can die from zinc deficiency even though it is has a normal concentration of zinc in its tissues, but it can respond rapidly to small amount of dietary zinc. The mechanisms by which the body stops growing in response to nutritional lack are similar to the hormonal picture seen in endocrine disease (reduction of the production of the hormonal mediators of growth, down-regulation of receptors, and reduction of protein synthesis). Growth failure is the clinical sign characteristic of a diet deficient in protein, zinc, magnesium, phosphorus, and potassium. Wasting may be also ascribed to toxins, infection, worms, or persistent diarrhea. Anorexia is another common response in nutrient deficiency. Only a supplementation diet with a balance of nutrients will promote rapid recovery.
 
Article
Plasma essential fatty acid (EFA) subclasses were determined in female and male patients with arthritis-like symptoms, healthy volunteers and endurance athletes. Samples were taken before and after nutritional therapy with the antioxidant ubiquinone and vitamin E (Q + E) on their own, or in combination with omega-3 EFAs as a fish oil concentrate (Q + E + n -3). Baseline data showed relatively high omega-6 EFA levels; (Q + E) nutritional therapy elevated predominantly omega-3 EFAs. (Q + E + n -3) caused only a marginal, further plasma eicosapentaenoic (EPA) increase but major effects on the EFA indices. These were linearly related to the estimated dietary EPA intake and might mirror a subsequently reduced risk for arachidonic acid cascade and suppressed inflammations.
 
Article
Dietary and plasma fatty acid composition is strongly related to the development of coronary heart disease (CHD). Since low-density lipoprotein (LDL) is the main vehicle for the uptake of lipids into the artery wall, it is important to know whether the fatty acid composition of this lipoprotein fraction differs in patients with CHD and healthy control subjects. The study comprised 59 newly presenting male patients with myocardial infarction (MI) and 94 healthy male control subjects. The cholesteryl esters (CE) of LDL of the MI group contained less 14:0 (p<0.0000001) and 16:0 (p<0.0001) but more 18:0 (p<0.0001) than those of the control group. For LDL phospholipids (PL), 14:0 (p<0.02) and 16:0 (p<0.0001) were higher in the MI group while 18:0 was lower (p<0.003). In addition, polyunsaturated acids 18:3n-3, 20:2n-6 and 20:4n-6 were all significantly lower in PL in the patient group. Triglyceride fatty acids showed little differences between the two groups. The most striking feature was the difference in the distribution of saturated fatty acids between the LDL CE and PL in the two subject groups (the ratio of PL saturates to CE saturates was 3.41 +/- 1.21 for the control group and 5.39 +/- 3.08 for the MI group (p<0.0000001). This study therefore demonstrates for the first time that highly significant differences occur in the relative proportions of LDL fatty acids in MI patients and control subjects and suggests the importance of dietary lipid intake and of lipid exchange during lipoprotein metabolism in producing LDL particles of low atherogenicity.
 
Article
The antioxidant activities of baicalin, which is a plant flavonoid, alizarin extracted from madder and green tea polyphenols extracted from green tea were studied in comparison with vitamin E or its water-soluble derivative, Trolox, in four different systems: (1) a p -iodophenol-enhanced horseradish peroxidase-luminol-perborate chemiluminescent system; (2) a hypoxanthine-xanthine oxidase-luminol chemiluminescent system; (3) lipid peroxidation in rat liver microsomes initiated by ADP-Fe2+ ; (4) lipid peroxidation in the liver of bromobenzene-intoxicated mice grouped randomly. Two chemical assays and one in vitro biological assay showed that the three natural extracts, in particular the green tea polyphenols, were very good antioxidants in their activity against iodophenol-derived phenoxyl radicals, superoxide anion radicals and lipid peroxidation in rat liver microsomes. However, the in vivo experiment showed that baicalin and alizarin were more effective than the green tea polyphenols and vitamin E in reducing the hepatic content of thiobarbituric acid-reactive substances and all three natural compounds were better than vitamin E in lowering the serum level of alanine aminotransferase in poisoned animals. It is evident that the activity of an antioxidant determined in any chemical system or even in an in vitro biological system such as rat liver microsomes can hardly represent the real activity in vivo .
 
Article
In a randomized, single-blind and controlled trial, the effects of guava fruit substitution were studied on vitamin C metabolism and coronary risk factors in 52 group A and 49 group B patients of essential hypertension with mild to moderate hypercholesterolaemia. At entry to the study, the mean age, mean body mass index, percentage male sex and risk factors were comparable. The dietary adherence to the guava intake was checked by a questionnaire and by the weighing of guava at 24 and 36 weeks into the follow-up. The study included a 24-week period of guava intake followed by a 12-week no-guava period. After 24 weeks of intervention, there was a self-imposed decreased intake of total fat and saturated fat and an increased polyunsaturated : saturated fat ratio in the diet in the group A patients. The total carbohydrate, soluble dietary fibre, potassium and vitamin C intakes were also higher in intervention group A than in group B. The increased consumption of vitamin C and other nutrients was associated with a significant net increase (p 0.001) in plasma ascorbic acid (45.3%, 95% confidence interval (CI) 21.6-96.6) in group A compared to group B. There was a significant net reduction in the serum total cholesterol (11.9%, 95% CI 3.5-19.5, p 0.01), triglycerides (8.1%, 95% CI 0.4-15.8, p 0.05), systolic blood pressure (5.0%, 95% CI 0.1-9.8) and diastolic blood pressure (6.4%, 95% CI 0.6-12.2) (p 0.05) and a significant net increase in the high-density lipoprotein cholesterol (8.9%, 95% CI 4.4-13.4%, p 0.01). At 36 weeks, 12 weeks after ceasing guava supplementation, there was an increase in the blood lipids and blood pressure from the levels at 24 weeks, indicating that the changes were due to the guava fruit intake. These changes in the vitamin C levels and risk factors may be due to an increased intake of soluble dietary fibre, potassium and vitamin C which may have decreased the coronary risk, leading to better prospects for the prevention of coronary artery disease.
 
Article
Background: Current evidence has established that statins are potent and effective agents with several pleiotropic effects in the treatment of coronary artery disease (CAD). Statins may have toxic effects, if given in higher doses and in combination. Design: Literature review. Methods: An Internet search and discussions with colleagues. Results: The 1990s have been called the ‘statin decennial’ and the Nobel laureates suggested ‘CAD: eliminated with statins’. Statins were also proclaimed as wonder drugs, influencing a wide range of physiological, biochemical and biological functions. The list appears to be long and includes hypolipidaemic, vasodilative, antithrombotic, antioxidant, anti‐inflammatory, antiproliferative, anticoagulant, angiogenic and bone formation inducing functions. In January 2002, the television network CNN announced in a dispatch from London that deaths resulting from the treatment of hypercholesterolaemia with cerivastatin (Baycol) have now exceeded 100. Concerned Americans discussed this issue in May 2002, and published advice with the intention of summarizing for professionals current knowledge about statin use, focusing on myopathy. The criteria for the diagnosis of myopathy are not concerned with the symptoms of patients in the absence of raised muscle enzymes. Coenzyme Q10 is not considered in prophylaxis because one study showed no decrease in coenzyme Q10 in muscles in the presence of toxicity, although some studies indicated a reduction in serum levels. Conclusion: Several studies have reported a significant reduction in serum coenzyme Q10 in patients taking statins. Such concern was also expressed by the International College of Cardiology at their meeting in April 2002; it was proposed that coenzyme Q10 should be considered in the prevention as well as the treatment of statin intoxication.
 
Article
A programme of investigation and treatment is described in two cases ofHIV-I infected male patients with AIDS symptomatology, who had been partially helped with AZT (Zidovudine). Under this programme, they were investigated for nutritional deficiencies and evidence of food and/or chemical sensitivities/intolerance which might aggravate or contribute to their condition. Subsequent nututritional supplementation and dietary advice has produced significant improvement.
 
Article
The allergy desensitization technique, known as "intradermal neutralization", was originally described by Dr H. Carlton-Lee. The procedure was later extended and modified by Professor J. B. Miller of Mobile, Alabama and currently is used extensively for treating allergic disease in humans, especially in the USA, but also in Canada, the UK and Australia. The technique has been shown in many clinical papers to be effective in humans as a means of desensitizing both food and biological inhalant allergens. It is also effective in chemical sensitivity. Although there have been sporadic reports of successful use in horses and other animals, this is the first to show a marked effect in equine asthma, otherwise known as chronic obstructive pulmonary disease or heaves. The results in equine urticaria are even better and there appears to be benefit in some cases of headshaking (equine rhinitis). The number of horses treated for sweet itch was too small to draw any conclusion. The positive effects shown in this study lend further support to those studies in humans, as a placebo effect in horses must be highly unlikely.
 
Article
Purpose: To measure the urinary excretion of amino acids in a large number of patients with chronic fatigue/pain disorders to determine whether distinct subgroups can be defined on the basis of the urine excretion patterns. Design: Laboratory-based survey, with comparison to prior control, chronic orofacial muscle pain and rheumatoid arthritis datasets. Materials and Methods: Urine samples and symptom data were collected from 1993 referral patients, with varying forms of chronic fatigue and pain conditions (including CFS and fibromyalgia), as part of their normal clinical evaluation over a period from June 1997 to October 1998. Each urine sample was analyzed for amino and organic acid content by gas chromatography-mass spectrometry (GC-MS). The urine profile data were analyzed by K-means clustering techniques. Results: It was found that six subgroups of patients could be delineated on the basis of the distributions of 13 amino acids measured in the urine. These groups were extremely well resolved by discriminant function analysis ( p <0.00001), and the canonical plot showed clear separation of all six groups. The groups were primarily differentiated by their concentrations of glycine, serine, alanine and glutamine/glutamic acid, but variations in the other amino acids contributed to the profile differences. Assessment of control and patient data compiled from previous studies revealed that all six phenotypes of amino acid homeostasis were present in healthy individuals, chronic myofacial pain patients and rheumatoid arthritis patients. The differences between the healthy individuals of a particular homeostatic phenotype and their corresponding chronically ill phenotype included the extent of amino acid depletion or excess, as well as alterations in non-protein amino acids (e.g. g -alanine) and organic acids. Conclusions: Six major types of amino acid homeostasis occurred in the patient cohort, each with its own specific nutritional requirements for amino acids. The same types of urinary excretion profiles could be observed in control subjects. The differences between the control and chronically ill patients depended on the extent of amino acid depletion or excess and variations in organic acid excretion. External influences such as pathogenic exposure, diet, genetic and environmental factors would also influence the final health status of the patient.
 
Clinical data and stage of the disease: mean (standard deviation)
Laboratory data on the cancer group and control group in men and women: mean (standard deviation)
Article
A total of 3810 patients were seen in hospital over a 2-year period. There were 101 patients with cancer of various organs of the body. These 101 cancer patients were compared with 100 age- and sex-matched control subjects selected from the same population. The aim was to find the relation between dietary and plasma levels of antioxidants and minerals and the risk of cancer. Dietary intakes were assessed by a 7-day food intake assisted questionnaire to find out previous intakes. The study showed that the plasma levels of antioxidant vitamins A, E and C and beta -carotene and the zinc copper ratio and zinc levels were significantly and inversely associated with the cancer group compared to the control subjects. The serum calcium level was also lower in the cancer group but the magnesium level was higher. Underlying these findings, the consumption of antioxidant vitamins A, E and C and beta -carotene, calcium and magnesium was significantly lower in the cancer group compared to the control subjects. The differences in intake indicated a higher risk of cancer with a lower consumption of antioxidant vitamins and fruit and vegetables and with a higher consumption of flesh foods and total visible fat. Lipid peroxides, malonyldialdehyde and diene conjugates, which are indicators of free radical stress and cell damage, were significantly higher in the cancer group compared to the control subjects. The findings suggest that the increased consumption of antioxidant and mineral-rich fruit and vegetables, in conjunction with a low fat diet, may provide protection against cancer. However, more studies are necessary to confirm our suggestions.
 
Article
In a randomized controlled double-blind trial, the effects of vitamin-mineral supplementation on violence and other serious antisocial behavior were studied for 3 months on 62 confined delinquents aged 13 to 17 years. A significant difference between 32 active and 30 placebo subjects was found for violent and non-violent antisocial behavior. The net difference in rule infractions between the active and placebo groups in violence was 28% (95% confidence interval 15-41%). This direction and magnitude of effect were seen with both violent and non-violent rule violations. Twenty-six habitually violent subjects donated pre- and post-intervention blood samples. Among 10 subjects who maintained their normal or low blood concentrations of vitamins throughout the trial, there was no marked change in violence (i.e. 39 acts during baseline and 37 during intervention). In contrast, the 16 subjects who corrected their low blood vitamin concentrations during intervention produced 131 violent acts during baseline and 11 during intervention. The correction of low blood vitamin concentrations with vitamin-mineral supplements improves brain function and significantly reduces violence among delinquents confined in correctional facilities.
 
Article
Purpose: There is good evidence that ascorbic acid (AA) status influences the onset of post-operative complications in intensive care patients. Light and room temperature cause the spontaneous oxidation of AA. Therefore, the stability of AA during modified sample preparation was investigated. Design: Prospective, single centre study. Methods: The AA plasma concentration was analysed in arterial and venous blood with added ethylene-diamine-tetra-acetic acid (EDTA) from 165 subjects. In addition, EDTA or heparin was added as an anticoagulant in venous blood of 79 subjects. Analyses were carried out using high performance liquid chromatography with ultraviolet detection. Results: In samples of arterial and venous blood with added EDTA it was observed that precision declined with increasing concentrations of AA. In venous samples with added heparin the correlation was low compared with venous samples with EDTA. Conclusion: Any change in our standard method of specimen collection (venous blood with added EDTA) results in AA plasma concentrations with questionable reliability.
 
Article
To analyze the relationship between the subjective assessment of nutritional status and anthropometric parameters, as well as the prognostic value of the subjective evaluation, the nutritional status of 280 patients was evaluated as follows on admission to a semi-intensive care unit: temporal muscle atrophy, Bichat's fat atrophy, upper and lower extremities muscle atrophy and subcutaneous fat atrophy. Each parameter was categorized into three degrees of severity and a nutritional score (NS) was obtained. We have also determined the mid-upper arm circumference (MUAC), the triceps skinfold (TSF), the mid-arm muscle area (MAMA), serum albumin and transferrin. During the hospital admission 88 patients died. We found a good concordance (82%) between subjective and objective (anthropometric data, fifth percentile criteria) assessments. Those patients who died showed significant lower values of MUAC, MAMA, TSF, serum albumin and transferrin; and higher neutrophil count, alpha-1-antitrypsin, ferritin, BUN and also NS. Discriminant stepwise analysis showed that the subjective evaluation predicts survival better than the individual anthropometric parameters.
 
Article
In previous studies, we have found that subjective nutritional assessment in critical-care patients shows short-term prognostic value. In these studies, nutritional assessments were performed by only one observer. The aim of the present study is to ascertain the prognostic value of subjective nutritional assessment of general medical patients when performed by different physicians. Training of the physician team was simple and consisted of two tutorial rounds of about 30 minutes each. The nutritional status of 394 patients (232 males and 162 females) was evaluated at admission by the physician on duty as follows: temporal muscle atrophy, Bichat's fat atrophy, upper and lower extremities muscle atrophy and subcutaneous fat atrophy; each parameter was categorized in three degrees and a nutritional score (the poorest value being 10 and 0 the best one) was obtained. Seventy-three patients died during this admission. Mortality rate was closely related to the nutritional score; 39% (39/99) of the patients with a score higher than 4 died vs only 12% with score values 4 or less. By logistic regression analysis, we found that the high relative risk of mortality (2.38; 95% IC 3.45–1.70) associated with a poor nutritional status is independent of other mortality-related variables such as age, serum albumin, leucocyte count, blood urea nitrogen and type of disease.
 
Article
The standard 3-week inpatient regime in the Airedale Allergy Centre for investigation of chronic symptoms involves a 5-day fast, followed by three single-food challenge meals a day. Endpoint titration [1] is used to curtail adverse reactions, and to test inhalants and chemicals. In 19 consecutive asthmatics, the peak expiratory flow rate (PEF) was consistent after some of the 646 food challenges, but fell after others, and was usually restored bv endpoint titration using dilutions of an extract of the trigger food. Bronchoconstriction was provoked and relieved by different dilutions of some of the chemicals and chemical mixtures tested sublingually. Results are demonstrated on continuous PEF charts, each covering nine or more challenges over several days: individuals differed in the profile of foods and chemicals provoking bronchoconstriction. The overall distribution of the maximum change in the PEF after each food challenge in nine patients on no asthma medication in the ‘clean’ conditions differed from the expected best-fit normal distribution (p < -0001); changes of more than 20 l/min were unlikely to have occurred by chance. the PEF fell after all types of food, but there were differences (p < 0.05), with more frequent drops (often delayed) after meat, fish and grains. When the PEF remained low after repeated adverse reactions, recovery most frequently occurred after a fruit meal (p < 0.0001). Genuine increases in the PEF were also noted.
 
Article
It has been known since the 1960s that exogenous progestogens and oestrogens (the pill and hormone replacement therapy (HRT)) increase the risk of both venous and arterial thrombosis. Claims that HRT prevents heart attacks in older women are mostly based on non-randomized epidemiological studies. Healthier women are selected for hormone taking and those with established diseases are excluded, either before or during the studies. Risks may be greatly underestimated. Thrombosis and heart attacks are evident after short-term exposure to hormones and relate mainly to immediate changes in blood vessels and clotting factors. Recent studies record increases of 4-400 times for thrombosis and heart attacks.
 
Article
Purpose: Previous studies in autistic children have shown that they have reduced levels of plasma sulphate as compared with age-matched control children and the aim of this study was to see if this reflected increased urinary sulphate loss. Design: Outpatient-based survey of autistic children and matched controls. Materials and methods: The children in the study were elected on the basis of ICD-10 criteria and a diagnosis of autism. Use of a behavioural questionnaire allowed children with autism to be divided into 3 subsets. Urinary excretion of sulphate, sulphite, thiosulphate and thiocyanate was measured in 232 autistic children and compared with values from 68 age-matched controls. Results: Autistic children excreted higher levels of sulphate, sulphite and thiosulphate, but reduced levels of thiocyanate. Conclusions: The significance of these altered parameters is discussed with respect to catecholamine metabolism, mucin formation, gastrointestinal hormone activation and sulphur anion metabolism.
 
Article
Purpose. Immune dysfunction has been associated with children with autism. One study found a beneficial response of intravenous gamma globulin (IVIG) therapy in autistic children. The present study further evaluated the administration of IVIG to these children. Design. This report shows the response of 26 autistic children who received IVIG over a 6 month period. Materials and methods. In documented autistic children, 400 mg kg−1 IVIG was administered each month for 6 months. Baseline and monthly Aberrant Behavior Checklists were completed on each child in order to measure the child's response to IVIG. Results. The participants' overall aberrant behaviors decreased substantially soon after receiving their first dose of IVIG. Further analysis of the total scores revealed decreases in hyperactivity, inappropriate speech, irritability, lethargy and stereotypy. However, 22 of the 26 children regressed to their pre‐IVIG status within 2–4 months of discontinuing the IVIG. Conclusions. Significant improvement occurred in autistic children receiving monthly IVIG. There is a reasonable rationale considering the risk/reward ratio to utilize IVIG therapy in children with autism. A well‐controlled placebo double‐blind study would be important to further clarify the use of IVIG in autism and its duration of benefits.
 
Article
Purpose: To explore the possible manifestations of abnormal levels of either cysteine or sulphate, whether high or low, and the ratio between them, in human subjects. Design: A case–control study of the plasma cysteine and sulphate levels and cysteine/sulphate ratio in chronically ill patients. Materials and Methods: Eighty‐one chronically ill patients of a nutrition clinic were suspected of having abnormal levels of sulphate and/or cysteine. Their plasma was checked to determine their cysteine and sulphate levels and cysteine/sulphate ratio. These were compared with the results of 177 controls. They were grouped according to their results, and their symptoms were listed. Results: Only one patient had a ratio within the reference range, whereas 175 of the controls did. Patients already being treated with relevant nutritional supplements at the time of testing were less likely to have a ratio over 1000. Some close relatives shared abnormal test results, but manifested different symptoms. Conclusion: Patients with chronic conditions including myalgic encephalomyelitis, irritable bowel syndrome, migraine, arthritis, multiple chemical sensitivity and depression are likely to benefit from tests for cysteine and sulphate, and from treatment designed to improve these levels. Oral fish oil, vitamin B2, pantothenate and molybdenum, and Epsom salt baths may help patients with low sulphate. Vitamins B2 and B6, zinc and magnesium, and a low protein diet may reduce high cysteine levels. N‐acetyl cysteine, zinc and vitamin C may help those with low cysteine levels. Patients with abnormal levels of sulphate might be counselled against working in polluted conditions, where efficient sulphate conjugation is required, and against using pesticides. They might be advised to be cautious in their use of drugs, and possibly vaccines too. Further work is suggested, to investigate to what extent abnormalities in cysteine and sulphate levels are genetically determined, and to test the efficacy of the treatments outlined, both at improving the cysteine and sulphate levels, and health.
 
Article
A double blind study was performed on 13 patients with food intolerance, confirmed by elimination dieting and repeated challenge. Intradermal testing was performed at 1:500, using 10 commonly reacting foods and 10 which rarely gave reactions, a total of 260 tests. As compared with the results of challenge, intradermal skin tests were assessed as 57.5% accurate. The results are compared with other studies, and whilst single strength intradermal testing cannot be put forward as a valid test for food intolerance it is suggested that apparent “false positive” responses may be due to a mechanism akin to atopy in IgE allergy.
 
Article
Purpose: Antioxidant vitamin and coenzyme Q10 deficiency as well as oxidative damage have been observed in patients with chronic renal failure. In this study, we examine whether treatment with coenzyme Q10 can improve renal function in chronic renal failure. Design: Randomized, double-blind, placebo-controlled trial. Materials and Methods: Subjects ( n = 21) with available records of chronic renal failure on dialysis or not on dialysis (serum creatinine 5 mg dl -1 or above) were randomly divided into intervention ( n = 11) and control ( n = 10) groups by blindly selecting a card. The intervention group was administered coenzyme Q10 (60 mg thrice daily) and the placebo group inert fibre (cellulose, 1 g thrice daily) for a period of 4 weeks. Results: The coenzyme Q10 group showed a significant reduction in serum creatinine, blood urea and a significant increase in creatinine clearance and urine output compared to the placebo group after the 4-week trial period, while the baseline values of these parameters were comparable between the two groups. The frequency of dialysis and the proportion of subjects on dialysis were comparable at baseline. However, after 4 weeks, the subjects on dialysis were significantly fewer in the coenzyme Q10 group than the placebo group (36.2% vs. 90.0% , p < 0.02). Plasma levels of antioxidant vitamins A, E and C and beta-carotene showed a significant increase whereas thiobarbituric acid reactive substances, diene conjugates and malondialdehyde showed a significant reduction in the coenzyme Q10 group compared to the control group. Conclusions: Treatment with coenzyme Q10 improves renal function in patients with chronic renal failure and decreases the need for dialysis in patients on chronic dialysis. Long-term follow-up in a large number of patients would be necessary to confirm these results.
 
Article
Irritable bowel syndrome (IBS) is a common yet poorly understood functional bowel disorder. A multi-factorial aetiology has been proposed, and abnormalities in colonic motility, small bowel motility and visceral sensation have been observed experimentally. More recently, attention has turned to a quite distinct abnormality, namely psychological function. Studies have shown that for a significant proportion of the IBS population, co-morbid psychiatric disturbance may be aetiopathological, with the physical abnormalities described occurring in response to stress or anxiety induced experimentally. Others have suggested that psychological distress may occur as a result of severe gastrointestinal symptoms, and that psychosocial factors may be related to the presentation rather than genesis of the symptoms. Many of these studies contain methodological inadequacies which may adversely affect the results obtained. Comparison between studies, which may provide further insight, is often difficult due to inconsistencies in the experimental protocol and the non-standard ways in which data have been presented. It is likely, however, that differences between methodologies may, in part, explain the variations in results between studies.
 
Article
It is proposed that the necessary balance between received wisdom and innovation in the hormonal manipulation of breast cancer has been lost through the dominance of the randomized, controlled trial. This method of investigation has displaced, rather than complemented, other means of progress. It has encouraged the indiscriminate use of hormones, especially tamoxifen, without reference to selective receptor tests, both old and new. The history of hormone manipulations and the knowledge accumulated thereby are reviewed. Data collected in the Breast Study Centre are presented to support the contention that treatment progress can be evaluated without recourse to randomization. The results confirm received wisdom that about one-third of breast cancers are hormone dependent. At a time when oestrogen receptor testing was not readily available, a trial of tamoxifen in an unselected series of breast cancer patients resulted in measurable shrinkage in less than half the cases and in 17% produced measurable growth. The latter were poorly differentiated grade III tumours. A satisfactory response to hormones was found to be associated with highly differentiated tumours. Recent advances in immunohistochemistry enable detailed profiles of histological grade, hormone receptors, proliferation indices and other markers of tumour behaviour in formalin-fixed sections only a few microns apart. Treatment may be selected for the particular tumour and the response monitored. A database representative of the wide range of tumour types, growth rates and hormone dependence may then be accumulated. This approach leads to refinements in therapy in contrast to trial results, representing an average, that are not applicable to the next individual patient.
 
Article
There are good biological reasons for concern about the influence of oral contraceptives and/or hormone replacement therapy (HRT) on the risks of breast and ovarian cancer. Despite the widespread and growing use of exogenous hormones, epidemiological data are deficient, especially in relation to prolonged ( 10 years) use of combined oestrogen/ progestagen preparations. Most studies suggest that the relative risk of breast cancer, in particular, is increased by use of both oral contraceptives and HRT, that risk increases with duration of use and that it may be higher for combined preparations. It is uncertain whether a pre-existing high genetic risk of breast cancer is compounded by use of exogenous hormones. This is a serious issue since a small relative increase in a large risk will have a major effect.
 
Article
The diagnosis of schizophrenia is presently based on the phenomena of the disease—that is the delusions, hallucinations and thought disorder. These phenomena however may be common to many diseases. It is suggested that very often diseases within the body may be causative of the psychiatric symptoms and that these causes should be sought in every individual case.
 
Article
In 1987, workers in the kitchen of one of the teaching hospitals in Halifax, Nova Scotia began to experience symptoms of pruritus, folliculitis, wheezing, conjunctival irritation, sore throat and headache, all suggestive of an indoor air quality (IAQ) problem. Approximately 127 of 160 kitchen workers were affected over a 2-year period and the complaints included cognitive difficulties and reactivity to environmental irritants. Workers in other parts of the hospital developed increasingly serious problems, including bronchial hyperreactivity, nausea, diarrhoea, weight loss, hair loss, recurrent infections, myalgia and arthralgia as well as more sinister neurotoxic effects of memory loss, poor concentration, visual perceptual losses, peripheral paraesthesia, Raynaud's phenomenon, severe fatigue, dizziness and neuromuscular incoordination. Between 1991 and 1993, more than 700 workers, out of a total workforce of 1250, reported symptoms. Over 300 workers were off work for periods of from 3 months to 3 years and, at the time of writing, over 100 workers remain disabled and unable to work. During the course of this epidemic, it became clear that the clinical features did not readily fit into any widely accepted single disease category or syndrome. However, the ill health appeared to be related to IAQ problems in all buildings. It also became apparent that much of the symptomatology was similar to the condition known as multiple chemical sensitivity. The sick workers became intolerant of the hospital environment and their symptoms appeared to be precipitated by incitants such as chemicals, mould, dust, food, light or electromagnetic radiation. This state of ill health is described as environmentally induced dysfunction and the essential clinical features include chronic ill health for at least 3 months with evidence of dysfunction in multiple organ systems. The symptoms wax and wane, are provoked by exposure to certain environments (e.g. the workplace) and improve upon removal of triggers or irritants. Many of the workers improved when they stopped work and created a very clean environment at home. Most patients have cognitive impairment and evidence of autonomic nervous system dysfunction. Chemical sensitivity is an important part of this problem and recognition of the importance of this has to occur to allow research to take place and to assist in the treatment of those already afflicted and incapacitated by these problems. As a greater understanding is gained, it should be possible, in the future, to prevent problems of the same magnitude as reported here.
 
Article
Purpose: To evaluate whether food avoidance methods could be successfully applied to a primary care environment. Design: An open uncontrolled trial. Materials and Methods: A total of 76 patients were offered the food exclusion method. Of these, 45 patients chose to proceed with this method and record all symptom levels. All symptoms were equally weighted and the sum of all symptoms was used as a score for measuring overall patient progress. Results: The results showed that over 37 patients improved, with an average improvement of over 80% of symptom scores. The remaining eight patients showed no improvement. Conclusions: For suitable patients, dietary management, using exclusion methods, can be successfully employed at a primary care level, with similar success rates to those expected at hospital out-patient units.
 
Article
The glycemic index (GI) and triglyceride response were determined in 30 non-insulin-dependent diabetes mellitus patients who were given 50-g portions of five cereal and cereal-green leafy vegetable combinations conventionally consumed in India. These included rice in the form of flakes and puffs, wheat bhakri (wheat flour kneaded, rolled out and shallow fried), wheat bhakri stuffed with fenugreek and spinach leaves. Compared with the blood glucose response for a 50-g glucose load, puffed rice and wheat bhakri showed a higher GI whereas rice flakes and wheat bhakri stuffed with green leafy vegetables produced a much lower glycemic response.
 
Article
There is a lack of data on the glycaemic response of Indian foods, particularly that of South Indian foods. In South India the bulk comes from cereal-based carbohydrates. The glycaemic response of three different meals in 20 non-insulin-dependent diabetic volunteers was therefore assessed. Each meal was isocaloric and balanced. Each meal comprised 60% carbohydrate, 20% protein and 20% fat, varying only in the type of carbohydrate. The carbohydrate exchange in each meal (rice, wheat and ragi, which form important staple foods of South Indians) contributed 39% of the total calories of the meal. The wheat-based meal showed the lowest glycaemic response, followed by ragi. The results confirmed the important role played by wheat in diabetic diets because of its blood sugar-reducing properties.
 
Article
It is well recognized that obese children are very likely to become obese adults. Relatively few studies have investigated dietary habits and weight of primary school children from varying ethnic backgrounds. Five hundred and sixteen primary school children of ages from 8 to 14 years were studied. Schools were selected from four socioeconomic categories. Children were divided into two main ethnic backgrounds, either Australian or Southern European. Fifteen per cent of children were overweight while a further 15% were obese. Only 2% were severely underweight. Children of Southern European background were more likely to be overweight or obese. It was found that obese children consumed less energy than those who had normal weight. Suggestions are made as to how the obesity problem in primary school children could be encountered.
 
Article
Plasma total cholesterol levels totalling 16 758 from a workforce population of approximately 4000 were available for each of the years 1984 to 1988. These data were examined in conjunction with locally acquired solar radiation measurements for each month of the study period. There was an inverse relationship between solar radiation and cholesterol levels (r= −0.476, p=0.0007) for the four-year period. However, solar radiation can vary widely from year to year. In 1984, a good year for sunshine, the correlation was consequently stronger (r= −0.867, p=0.0003). This suggests that solar radiation accounted for 75% of the observed cholesterol variability for that year. Subsequent years experienced less solar radiation but, with the exception of 1986, demonstrated significant inverse correlations, being r= −0.648, p=0.022 and r= −0.579, p=0.0466 for 1985 and 1987 respectively. Since there can be marked regional differences in sunshine with our maritime climate, these findings may explain the geographical distribution of coronary heart disease (CHD) in the United Kingdom (UK). The high mean annual cloud cover, with relatively poor available solar radiation levels, may aso reveal why the UK has such a high population mean cholesterol level and incidence of CHD.
 
Article
The effects of dietary intake of fish on plasma cholesterol, triglycerides and lipoproteins were assessed in 30 patients diagnosed with coronary heart disease (myocardial infarction or angina pectoris). Biochemical determinations were performed while the subjects consumed their habitual diet (DI)' after eight weeks on a unified diet (D2), and after four weeks on a diet rich in jkh fat (D3), the fish diet significantly increased high density lipoprotein cholesterol (from 28.3± 1.0 mg dl−1 to 35.1± 1.4 mg dl−1 with diets D2 and D3 respectively, p < 0–001), significantly reduced low density lipoprotein cholesterol (from 172.9 ± 6.3 mg dl-1to 158.0 ±5.2 mg dl-1with diets D2 and D3 respectively (p < 0.001), and had no significant effect on plasma triglycerides or total cholesterol. the findings suggest that increasing dietary fih can significantly modify high and low density liprotein cholesterol, which are beneficial in preventing and treating coronary heart disease.
 
The boy before treatment.  
The boy after 4 weeks of treatment.  
Article
A 5-year-old male child presented with convulsive seizures, mental retardation and cutaneous angiofibroma of about 4 years' duration. A physical examination revealed that he was unable to sit up, stand and walk. He had fine wart-like lesions on the cheek and forehead. A systemic examination showed no abnormality. A computerized axial tomography scan revealed calcification at the head of the right caudate nucleus without associated edema. Irregular calcification was also seen adjacent to the posterior part of the body of the left lateral ventricle. He showed improvement in mental deficiency and seizures on treatment with coenzyme Q10 (90 mg day 4 ) and fish oil (Eicosapataenoic acid (EPA) 1.08 g + Docosahaexenoic acid (DHA) 0.72 g day -1 ) within 12 weeks of follow-up.
 
Article
The Royal College of General Practitioners' Oral Contraception Study, started in 1968/9, is reviewed. The limitations of any cohort study and the particular characteristics of this study mean that only large effects on common diseases are likely to be detected. Effects on conditions that might be subject to reporting bias, and on those, like cancers, which may only appear after a long time lag, are particularly unlikely to be estimated with any accuracy. The study does show a clear connection between oral contraceptive use and cardiovascular disease. It also suggests a range of conditions, including depression and some cancers, whose incidence might be increased by oral contraceptive use, and a few whose incidence might be decreased.
 
Article
The hypothesis is advanced that when a living organism is exposed to a toxic chemical, the appropriate detoxifying reactions will not take place unless the toxic stimulus is above a certain threshold level. It is proposed that exposures below this level give rise to the phenomena of multiple chemical sensitivity (MCS). Supporting arguments are given based on thermodynamics and biological parallels, and it is shown that the idea gives simple explanations for some of the paradoxical symptomatology of MCS. MCS is described as the complement of allergy, and it is suggested that the theory could lead to new approaches to the treatment of MCS.
 
Article
633 London women who were given nutritional counselling in the last two trimesters of pregnancy had babies who were on average 78 g heavier than 266 controls who were not counselled. the birth head circumference and birth length of the babies of the counselled women were not significantly different to the controls. of the 633 counselled women, 211 received a vitamin-mineral supplement and 205 also received a supplement to provide additional linoleic acid. Neither supplemented group had babies with dimensions significantly different to the babies of 217 women who received counselling only with no supplemenets. Earlier papers showed very significant correlations between maternal nutrient intakes during the first trimester and birth dimensions; these strong associations contrast with the very modest effects of dietary supplementation in the second and third trimesters of pregnancy and emphasize the overriding importance of maternal nutrition around the time of conception. It is concluded that the variations in newborn size are mainly determined before the end of the first trimester.
 
Article
Milk may serve as a vector for the transmission of substances of extrinsic origin which can be potentially toxic to the consumer. These toxins may originate in cow's milk from the ingestion of plants known to contain toxic substances or feeds contaminated with mycotoxins, or residues of pesticides or herbicides. Harm to the consumer of cow's milk may also result from the use of antibiotics used for the treatment of disease in cows or for their growth enhancement. In the case of human breast milk, the routes of exposure can be quite diverse. These include milk derived from nursing mothers who have received medication in the form of drugs or antibiotics. Non-medical contaminants may originate from the mother's excessive use of alcohol, coffee, or tobacco. Other routes of contamination include the diagnostic use of radioisotopes, the transmission of allergens such as peanuts, mercury poisoning from dental fillings or fish, and contamination of the mother's diet with pesticide residues.
 
Article
Western medicine is expensive and technologically sophisticated; Third World medicine is simpler and cheaper; nuritional medicine is too easily neglected by both of these. All of them have a vital role to play in the future of medical science and practice in an era when the delivery of health care is a political issue as much as a medical one, and when the adverse consequences of progress are liable to return to haunt us. We must learn to co-operate, not to squabble
 
Article
We investigated the effects of dietary α-tocopherol and polyunsaturated fatty acids (PUFA) on ischemia-reperfusion injury and cardiac lipid composition. Rats were fed corn oil (CO) diets either deficient (CO-E) or supplemented (CO+E) with RRR-α-tocopherol (100 IU kg-1 diet), or butter oil (BO) diets either deficient (BO-E) or supplemented (BO+E) with RRR-α-tocopherol (100 IU kg-1 diet). Intact rat hearts were subjected to ischemia before reperfusion. Dietary RRR-α-tocopherol supplementation contributed to recovery of aortic output, cardiac output and diastolic pressure after ischemia-reperfusion. In contrast, the type of dietary fat did not influence most measures of cardiac recovery. RRR-α-tocopherol levels in cardiac tissues and plasma were significantly higher for rats fed the BO+E diet than for rats fed the CO+E diet. In contrast to plasma, PUFA in cardiac tissues were maintained at a high level even when rats were fed BO containing diets. Our results suggest that dietary RRR-α-tocopherol, but not dietary PUFA levels, modulate oxidative damage to intact rat hearts during ischemia-reperfusion.
 
Article
Purpose. To develop an overview of the kinds of disease that can be exacerbated by excessive/misplaced iron; to briefly consider mortality data on iron‐loaded persons; and to summarize methods for the prevention and therapy of iron loading. Design. Literature review. Materials and methods. A survey of clinical and research medical journals of the past decade was carried out. The diseases were categorized by medical specialty and by currently proposed types of iron association. Results. A remarkably diverse assemblage of diseases have been reported to be associated with and/or exacerbated by excessive or misplaced iron in specific tissue sites. Reduced longevity was associated with iron loading in two studies, but not in a third. Behavioral factors, as well as genetic modifiers, have been described that can result in an increase in inhaled, ingested and injected iron. Conclusions. Our present knowledge strongly indicates that methods for the reduction of iron loading could contribute considerably to the improved health and longevity of human populations.
 
Article
The limitations of the acute intervention medical model in dealing with the prevention and treatment of chronic and killer diseases are discussed. It is argued that it is more useful to approach patients as individuals who have failed to adapt adequately to the sum of their unique environmental challenges. Transcripition of the genome is an exquisitely nutrient-dependent, toxin-sensitive process. Failure of accurate transcription of the genome is a fundamental mechanism in the development of ill-health. The work of Weatherall, Williams and Garrod is highlighted
 
Article
The human gut plays host to a complex system of micro-organisms. The number of cells in this biomass is greater than the number of human cells in the body. Normal intestinal flora provide a wide variety of benefits to the host organism, including inhibition of pathogenic organisms, nutritional and biochemical effects, and modulation of the immune system both locally and systemically. Although the microflora of an individual are normally highly stable, they can be modified by diet, disease and pharmacological agents. There is growing evidence that these organisms can have significant impact on health and disease, and an understanding of gut ecology may therefore be relevant to clinical practice. This paper reviews the history and literature of intestinal microbiology
 
Article
RBC and serum folate were determined in 20 schizophrenic patients not taking neuroleptic drugs, 63 treated with neuroleptic drugs, and 41 healthy control subjects. the results showed significantly lower concentrations of folate in both RBC and serum in patients who were being treated with neuroleptics compared with those not being treated. Although not significant, lower levels of folate were found in patients who were on more than one drug than in those given a single medication. Moreover, patients who were ‘actively ill’ had lower levels of RBC and serum folate compared to those who were ‘fairly well‘. This was true for both neuroleptic-treated as well as untreated patients. in the neuroleptic-treated group, patients who were ill for 2 years and more had significantly lower concentrations of both RBC and serum folate than more recently ill patients. Although not significant a slow decline in RBC and serum folate was seen with the increasing chronicity of illness in the neuroleptic-free group. Even with comparable chronicity of illness, significant differences were found between neuroleptic-free and neuroleptic-treated patients. As expected, a significant correlation was found between RBC and serum folate in all the three groups studied. This study suggests that folate deficiency does not cause schizophrenia, but the severity of the disease, the chronicity of the disease as well as the medication given to treat it lead to folate deficiency. It is proposed that folate supplements should be given to such patients together with their other medications.
 
Top-cited authors
David G Savage
  • Columbia University
Jeffrey Bland
  • Personalized Lifestyle Medicine Institute (PLMI)
William Rea
  • Environmental Health Center - Dallas
Steve Wynn
  • Northeastern Oklahoma A&M College
Michael Crawford
  • Imperial College London