Michael G.W. Camitta, MD
 https://medicine.duke.edu/faculty/michael-gw-camitta-md For groups of individuals there is strong evidence of a dose response relationship between increased consumption of sodium as sodium chloride and higher levels of systolic allergy treatment xerosis order 4 mg periactin fast delivery, diastolic and mean blood pressure (Sacks et al allergy like virus buy periactin 4mg with amex, 2001) allergy forecast boston purchase discount periactin line. The character of the dose response can be modulated by a range of factors which include other components of the diet allergy symptoms lose voice discount periactin master card, relative weight, and level of physical activity, as well as fixed factors which include age, gender and genotype. It is not possible to determine a threshold level of habitual sodium consumption below which there is unlikely to be any adverse effect on blood pressure. The evidence for adverse cardiovascular effects of sodium, which is supported by number of prospective studies, indicate an association of increased risk of morbidity and mortality from cardiovascular diseases, including coronary heart disease and stroke, with increasing sodium intake. While it has been suggested that the magnitude of the observed effects was greater than could have been expected from a simple effect on blood pressure, there is no direct evidence for this, and evidence that high sodium intake may have a direct adverse effect on left ventricular structure and function, independent of any secondary effect due to changes in blood pressure, is not conclusive. The current levels of sodium consumption as sodium chloride have been associated directly with a greater likelihood of increased blood pressure, which in turn has been directly 441. Low urinary sodium is associated with greater risk of myocardial infarction among treated hypertensive men. The effect of sodium balance on sweat sodium and plasma aldosterone concentration. Value of echocardiographic measurement of left ventricular mass in predicting cardiovascular morbid events in hypertensive men. Evaluation of the aetiological role of dietary salt exposure in gastric cancer and other cancers in humans. Prenatal and early postnatal sodium chloride intake modifies the solution preferences of adult rats. Urinary sodium excretion and blood pressure in children: absence of a reproducible association. Lowering blood pressure: a systematic review of sustained effects of non-pharmacological interventions. Cause and effect between concentration-dependent tissue damage and temporary cell proliferation in rat stomach mucosa by NaCl, a stomach tumor promoter. Dietary sodium restriction rapidly improves large elastic artery compliance in older adults with systolic hypertension. Effects of sodium restriction on blood pressure, renin, aldosterone, catecholamines, cholesterols, and triglyceride: a meta-analysis. Influence of an enriched dietary sodium chloride regime during gestation and suckling and post-natally on the ontogeny of hypertension in the rat. Dietary sodium intake and subsequent risk of cardiovascular disease in overweight adults. The National Diet and Nutrition Survey: adults aged 19 to 64 years, volume 3 vitamin and mineral intake and urinary analytes. Epstein-Barr-virus-specific IgA and IgG serum antibodies in nasopharyngeal carcinoma. Increased blood pressure in schoolchildren related to high sodium levels in drinking water. Systematic review of long term effects of advice to reduce dietary salt in adults. Developmental sensitivity to high dietary sodium chloride in borderline hypertensive rats. Some Naturally Occuring Substances: Food Items and Constituents, Heterocyclic Aromatic Amines and Mycotoxins. Iishi H, Tatsuta M, Baba M, Hirasawa R, Sakai N, Yano H, Uehara H, Nakaizumi A (1999). Relation of left ventricular mass and geometry to morbidity and mortality in uncomplicated essential hypertension. The association between blood pressure, age, and dietary sodium and potassium: a population study. In Comparative Quantification of Health Risk: global and regional burden of disease attributable to selected major risk factors. Effect of diet and Helicobacter pylori infection to the risk of early gastric cancer. Stratifying the patient at risk from coronary disease: new insights from the Framingham Heart Study. Cardiovascular and humoral responses to extremes of sodium intake in normal black and white men. Obesity modifies the relationship between ambulatory blood pressure and natriuresis in children. MacMahon S, Peto R, Cutler J, Collins R, Sorlie P, Neaton J, Abbott R, Godwin J, Dyer A, Stamler J (1990). Part 1, Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Marinobufagenin may mediate the impact of salty diets on left ventricular hypertrophy by disrupting the protective function of coronary microvascular endothelium. Effect of reduced dietary sodium on blood pressure: a meta-analysis of randomized controlled trials. Heterogeneity of blood pressure response to dietary sodium restriction in normotensive adults. Opinion of the Scientific Panel on Dietetic Products, Nutrition and Allergies on a request from the Commission related to the tolerable upper intake level of chloride. Increased sodium concentrations in drinking water increases blood pressure in neonates. Age-specific relevance of blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Renal sodium handling in normal humans subjected to low, normal and extremely high sodium supplies. Epstein-Barr virus activation in Raji cells by extracts of preserved food from high risk areas for nasopharyngeal carcinoma. Salt and salted food intake and subsequent risk of gastric cancer among middle aged Japanese men and women. Tuomilehto J, Jousilahti P, Rastenyte D, Moltchanov V, Tanskanen A, Pietinen P, Nissinen A (2001). Urinary sodium excretion and cardiovascular mortality in Finland: a prospective study. Salt intake, cured meat consumption, refrigerator use and stomach cancer incidence: a prospective cohort study (Netherlands). Prevention and Management of Hypertension, World Health Organization, Regional Office for the Eastern Mediterranean, Alexandria. Estimates of habitual dietary intakes in European countries are on average around 1000-1500 mg/day, ranging up to about 2600 mg/day. Adverse effects of excessive phosphorus intake, such as hyperphosphatemia, leading to secondary hyperparathyroidism, skeletal deformations, bone loss, and/or ectopic calcification have been reported in animal studies. However, such effects were not observed in studies in humans, except in patients with end stage renal disease. In these studies no evidence was found for effects on markers of bone remodelling and the Panel does not consider these to be adverse effects. Similarly, the Panel found no convincing evidence to support suggestions that high phosphorus diets would aggravate the effects of a state of secondary hyperparathyroidism induced by inadequate calcium intakes, or an inadequate vitamin D status. Gastrointestinal symptoms, such as osmotic diarrhoea, nausea and vomiting, have been seen in some healthy subjects taking phosphorus (phosphate) supplements with dosages >750 mg/day. The Panel considered that these are not a suitable basis to establish an upper level for phosphorus from all sources. The Panel concludes that the available data are not sufficient to establish an upper level for phosphorus.
There is Both hila are markedly elevated indicating soft tissues masses increased lucency at the apices allergy forecast in houston tx generic periactin 4mg overnight delivery, in keeping bilateral upper zone volume loss allergy treatment with laser discount periactin master card. These are outlined by thin the medial aspect of the right Below the Diaphragm: Normal crescents of air allergy medicine non antihistamine buy cheap periactin 4mg line. Comparison with previous imaging would be useful to assess the differential diagnosis for upper lobe fbrosis includes for progression of changes allergy panel buy periactin uk. Hila: Enlarged, dense left hilum Normal size, shape, and position of right Behind Heart: Right retrocardiac mass hila. The left hilum is enlarged and dense, Costophrenic Angles: Normal consistent with lymph node enlargement. There is evidence of mediastinal lymph node enlargement (widened right the patient should be referred to respiratory/oncology paratracheal stripe, dense left hilum and right retrocardiac services for further management, which may include biopsy mass). Treatment, which may include surgery, represents malignant spread via the lymphatics (lymphangitis radiotherapy, chemotherapy, or palliative treatment, will carcinomatosis). The key to interpreting X-rays is having a systematic method for assessment, and then getting lots of practice looking at and presenting X-rays. The best-selling core radiology text the Unoffcial Guide to Radiology received recognition from the British Medical Association, the British Institute of Radiology and the Royal College of Radiologists for its unique approach to teaching. Most importantly, the clarity of the on-image labelling gives immediate feedback, enabling the reader to make sense of each radiograph. Like the other successful books in the Unofficial Guide series, this book builds on real clinical cases that you are likely to encounter during your undergraduate training. Each image is presented clearly with the relevant anatomical features and abnormalities highlighted clearly and set in the context of the pathophysiology. Professor Simon Maxwell, Professor of Student Learning, University of Edinburgh What I like about the book is the way in which 100 chest X-rays are systematically annotated to highlight all the features that need to be taken into account and reports are also included. I think this will be a really useful book for students and early stage trainees, as well as for doctors who are revising for exams or simply want to practice interpreting X-ray findings. Professor Judy McKimm, Professor of Medical Education and Director of Strategic Educational Development, Swansea University School of Medicine this is probably the easiest way of learning the basics of chest X-ray interpretation. An excellent introduction for the beginner and a superb way of revising the subject for those of us who are rather rusty. In truth, achieving this degree of accuracy is unrealistic and information is always lost in the process of such scoring. As a result, despite a myriad of scoring systems having been proposed, all such scores have both advantages and disadvantages. Part of the reason for such inaccuracy is the inherent anatomic and physiologic differences that exist between patients. A Coma Score of 13 or higher correlates with a mild brain injury, 9 to 12 is a moderate injury and 8 or less a severe brain injury. It is composed of three parameters: Best Eye Response, Best Verbal Response, Best Motor Response, as given below: Best Eye Response (4) Best Verbal Response (5) Best Motor Response (6) 1. Originally convened in 1987, these scoring systems are modified and updated as deemed appropriate by the Committee. These scales provide a common nomenclature by which physicians may describe injuries sustained and their severity. Since this time it has been revised and updated against survival so that it now provides a reasonably accurate ranking of the severity of injury. Injuries are ranked on a scale of 1 to 6, with 1 being minor, 5 severe, and 6 a nonsurvivable injury. This is calculated as the sum of the squares of the top three scores regardless of body region. This assumes, however, that the non-clinical hospital coders are able to accurately interpret and document the injuries sustained. It is scored from the first set of data obtained on the patient, and consists of Glasgow Coma Scale, Systolic Blood Pressure and Respiratory Rate. If the patient is less than 15, the blunt index for b3 (Age) is used regardless of mechanism. If the vessel injury is within 2 cm of the organ parenchyma, refer to the specific organ injury scale. Thoracic and lung ultrasound have become a rapid and accurate method of diagnosis of hypoxic diseases. Recent findings Many international critical care societies published guidelines on the use of ultrasound in the installation of central venous access. Lung ultrasound has shown its superiority over conventional chest radiography in the diagnosis of many disorders of significant importance in anesthesiology, particularly the pneumothorax. The aim of this review is to describe the basic lung ultrasound technique and the knowledge required in order to diagnose and treat the hypoxic patient. Emphasis is on disorder such as pleural effusion, alveolar interstitial disease, as well as pneumothorax, which is of particular importance in the field of anesthesiology. The American Society of Anesthesiology, the American Society of Echocardiography, and the lung disease, and pleural effusion. Multiple international critical care societies established guidelines concern ate the hypoxic patient. Ultrasound is a tool widely used in aDepartment of Emergency Medicine, Hopital du Sacre-Coeur de Mon the evaluation of the hypoxic patient. Indeed, treal, Universite de Montreal, bDepartment of family and emergency multiple studies have been published in the last c medicine, Universite de Montreal. The transducer is apposed perpendicular to Its use has been shown to significantly change the the long axis of the ribs in order to obtain an image diagnosis and treatment of the hypoxic patient in the of two ribs cut in a transverse fashion (Fig. The parietal and visceral necessary in order to perform thoracic and lung pleura creating this interface move in a synchronous ultrasound accurately and safely. Lung ultrasound can be done in a sitting or the lung parenchyma located under the pleural supine patient. All zones planes that are used: the sagittal and the coronal on each hemithorax must be scanned in order to plane (Fig. Both abdominal rooms are in a supine position, this approach will lateral upper quadrants can also be examined in be discussed here. Different imaging modalities are used ciples in the identification of specific disorders are depending on expected disorder. The linear array (a), the phased array (note the simple pleural effusion) (b), the convex (c) and the transesophageal echocardiography transducer (note the complex pleural effusion) (d). It is often quoted that lung ultra Ultrasounds are sound waves with a frequency sound makes facts out of artefacts. After lung sliding, higher than what can be perceived by the human the most common artefacts in lung ultrasound are ear. The A line energy absorbed as well as the time between the artefact is the single or multiple horizontal reflec emission and reception of the ultrasound wave by tions of the pleural interface. The emitted ultra the transducer, the software is able to generate sound wave is reflected multiple times by the an image depicting the underlying structures. This back and forth phenomenon Ultrasounds are completely reflected by air, so it is gives a false impression to the imaging software that impossible in theory to see the air-filled lung paren the pleural interface is deeper. In both normal and abnormal conditions, ated by a distance equivalent to the thickness of the the thoracic cavity and the lungs may contain some subcutaneous tissue between the ultrasound probe physiologic or pathologic fluid. A lines are present in a the relation between the ultrasound wave and the normal lung as well as in the presence of a pneumo air contained in the alveolar interstitial space of the thorax (Fig.
Effects on prothrombin time have been reported in patients taking sufficient nicotinic acid to cause hepatic toxicity allergy medicine over the counter non drowsy order periactin australia. Elevated prothrombin times have been reported in a small number of cases milk allergy symptoms in 5 year old purchase periactin, which were associated with only mild elevation of transaminase levels so that blood-clotting disorders may become the limiting sign of hepatotoxicity in some cases allergy testing severe reaction buy discount periactin 4 mg online. In contrast to the studies that have reported abnormal liver function in patients treated with nicotinic acid allergy shots protocol buy discount periactin 4 mg on-line, a small study in the group of 30 patients with hyperlipidaemia who were given slow release nicotinic acid at 1 g/day for 2 months and then 2-3 g/day for 10 months reported a low incidence of symptoms other than skin flushing (which had an incidence of 26. There was no evidence of hepatic abnormalities as indicated by changes in serum aminotransferases, alkaline phosphatase or antipyrine test results (Chojnowska-Jezierska and Adamska-Dyniewska, 1998). A large number of studies have defined the efficacy and tolerability of both conventional and sustained or controlled-release nicotinic acid in the treatment of hypercholesterolaemia and hyperlipidaemias. The data from these studies provide adequate evidence of the hazard identification and some evidence of dose-response characterisation. A major problem with the use of such data for establishing an upper level is that the doses investigated were restricted to those that showed clinical efficacy in the conditions being treated (mostly 3 g/day), and there are few data available at lower levels (Rader et al, 1992). Hodis (1990) reported a case of acute hepatic failure, which was ascribed to treatment with 500 mg per day nicotinic acid, however there was no repeat challenge or other data to support causation (other than an absence of other recognised reasons). Glucose intolerance Although hyperglycaemia is a relatively rare side-effect associated with high doses of nicotinic acid, it can be of clinical significance. Administration of 3 g of nicotinic acid per day for 10-14 days to volunteers resulted in an increase in fasting blood glucose and immuno-reactive insulin in serum (Miettinen et al, 1969). An increase in blood glucose concentrations, glycosuria, elevated serum ketone bodies, and an increase requirement for hypoglycaemic medication were reported in 6 patients with diabetes mellitus, who were receiving between 1 g and 3 g of nicotinic acid daily for a period of 2 weeks or more (Molnar europa. Gray et al (1994) reported a high incidence of hyperglycaemia in elderly hyperlipidaemic patients who had been treated with high doses of nicotinic acid (average dose 1. Schwartz (1993) described a patient who was hospitalised with severe hyperglycaemia following treatment with 3 g of nicotinic acid per day for 4 months; administration of insulin and oral hypoglycaemics reversed and stabilised the blood glucose levels. Other effects and overall dose-response relationships Thrombocytopaenia, which resolved on cessation of nicotinic acid treatment, was reported in a single patient who developed hepatitis 10 years after the initiation of nicotinic acid treatment (Reimund and Ramos, 1994). The plasma concentrations of homocysteine were increased by 55% in patients with peripheral arterial disease who were treated with nicotinic acid (Garg et al, 1999). The 52 patients were a subgroup from a multicentre study in which patients were given increasing doses of 100, 500 and 1000 mg per day over periods of 3-4 weeks (in order to identify patients who tolerated nicotinic acid), following which the subjects were randomised to receive either placebo or nicotinic acid (up to 3 g per day). The plasma concentrations of homocysteine were measured at baseline, at randomisation and at 18 and 48 weeks after randomisation. After randomisation the levels increased further in those receiving nicotinic acid (to about 20 M at 18 and 48 weeks; n=25 and 24, respectively), but decreased in those on placebo (to about 12 M at 18 and 48 weeks; n=21 and 22, respectively). The clinical significance of this is unclear, but elevated plasma homocysteine is a recognised risk factor for coronary artery disease. Severe reversible cystoid macular oedema was reported in 3 patients receiving high-doses of nicotinic acid (Gass, 1973). A survey of 116 patients who had received nicotinic acid (3 g or more per day) for treatment of hyperlipidaemia and a similar number of patients who were not treated with nicotinic acid revealed an increased incidence of decreased vision associated with sicca syndromes, eyelid oedema or macular oedema (Fraunfelder et al, 1995). Because the majority of the data arise from studies designed to investigate the hypolipidaemic action of nicotinic acid, most of the data relate to doses of 1 g/day or more. In consequence, there are few data available on the tolerability and toxicity of doses less than 500 mg/day. In general the main adverse effect reported at intakes below the 500 mg/day has been flushing which is generally self-limiting in relation to continuation of treatment or intake of nicotinic acid. A retrospective review of 21 such cases reported similar adverse effects to those found in adults, with 6 children showing reversible dose-related elevations in serum transaminases, and 8 children who discontinued treatment because of flushing, abdominal pains and/or elevated serum transaminase levels. Hepatitis was reported in subjects with very high doses on a mg/kg bw/day basis (50, 67, 41, 34, 48 and 39 mg/kg bw/day) (Colletti et al, 1993). Almost one-half of the subjects discontinued treatment because of adverse effects with poor glycaemic control occurring in 41% of patients with diabetes mellitus. These data indicate that the spectrum of toxicity is similar in elderly and young adults. The side-effect profile of wax matrix sustained-release nicotinic acid was studied in groups of younger (<50 years) and older (50-70 year old) hypercholesterolaemic subjects. The study was a randomised double-blind placebo controlled design of 8 weeks duration with doses of 1. Clinically significant side-effect included flushing, itching, tingling, upper gastrointestinal symptoms, constipation, diarrhoea, dizziness, palpitations and blurred vision; the overall incidence of adverse effects was similar in the two difference age groups (Keenan et al, 1992). Vasodilatory effects (flushing) the flushing reported with nicotinic acid does not occur following nicotinamide, either given as an intravenous injection (Bean and Spies, 1940) or when it is given orally at high-doses to patients with diabetes (Knip et al, 2000). Gastrointestinal effects Gastrointestinal effects are rare following high-dose treatment with nicotinamide (Knip et al, 2000). Nausea was reported in a single subject who had taken nicotinamide 3 g daily followed by 9 g per day for several days (Winter and Boyer, 1973). Hepatotoxicity Only one patient has been reported to have developed hepatitis after nicotinamide alone, and this subject had been given 3 g daily followed by 9 g per day for several days (Winter and Boyer, 1973); other subjects who developed liver disease after nicotinamide had also received prolonged treatment with nicotinic acid (see Rader et al, 1992). Increased serum transaminase levels were reported for 17 out of 41 children with attention deficit disorders treated for 12 weeks with daily doses of 3 g nicotinamide, in combination with 1. Whether this hepatotoxic effect was related to the high dose of nicotinamide, or to the combination with the high doses of pantothenic acid, vitamin C and pyridoxine, cannot be concluded from this study, and therefore, this study cannot be used in risk assessment of nicotinamide. The supplementation trials on the use of nicotinamide to prevent or delay the development of diabetes mellitus have not reported hepatitis as an adverse effect (Knip et al, 2000); however these have involved smaller number of subjects, have been of shorter duration and at lower doses than the trials on the use of nicotinic acid for the treatment of hypercholesterolaemia. Ten newly diagnosed Type 1 diabetic patients were given 1 g/day for 45 days (Mendola et al, 1989), and compared over the following year with a group who were treated with placebo; the authors reported that no adverse effects were observed when physical, biochemical and haematological parameters were considered (no details of the tests were given and the main aim of the paper was to study efficacy). A group of 35 patients, aged 6 to 18 years, were given either placebo (n=17), or up to 1. No adverse effects were reported in a group of nine Type 1 diabetic patients with ketosis given 3 g of nicotinamide per day, three of whom were treated for up to 12 months, compared to 7 similar patients given placebo (Vague et al, 1987). Glucose intolerance Nicotinamide has been studied in relation to reducing the risk of the development of diabetes mellitus; none of the studies (see above) has reported a worsening of symptoms in the treated groups. Other effects and overall dose-response relationships There have been no other adverse effects reported following the administration of nicotinamide in trials in patients with diabetes. These different doses can be calculated on a body weight basis using the data on body weights or ages in the different publications; the doses approximate to 17 mg/kg bw/day (Mendola et al, 1989; average age 18. Nicotinic acid the more severe forms of toxicity of nicotinic acid, as described above, occur principally at doses of greater than 500 mg/day. The limiting adverse effect at lower doses is flushing, and this has been reported at much lower intakes than the other adverse effects. The most severe and potentially life threatening adverse effects, such as hepatotoxicity, occur at doses one order of magnitude higher than have been reported for flushing. The dose of free nicotinic acid reported to produce flushing consistently in clinical studies is 50 mg/day (Sebrell and Butler, 1938; Spies et al, 1938). Spies et al (1938) reported a 5% incidence of flushing after a single oral dose of 50 mg nicotinic acid and a 50% incidence at 100 mg. The available data indicate that flushing would be unlikely to occur repeatedly in subjects given less than 50 mg/day, but occasional flushing was reported by Sebrell and Butler (1938) at a dose of 30 mg of nicotinic acid daily. A tolerable upper intake level for nicotinic acid of 10 mg/day is based on the available data indicating occasional flushing at 30 mg per day, using an uncertainty factor of 3 to allow for the fact that a slight effect was reported, and that the study was performed in a small number of subjects, but taking into account the steep dose-response relationship. This upper level is 300-fold below the dose frequently used clinically for the treatment of hypercholesterolaemia (3 g/day) and which is associated with a high incidence of serious adverse reactions. The only reports of flushing associated with the ingestion of nicotinic acid with food have occurred following the addition of free nicotinic acid to food prior to consumption. Although flushing might be considered a minor health effect, it has been used as the basis for setting the upper level for nicotinic acid, because of concerns about the possibility of a transient hypotensive episode, especially in the elderly. The upper level of 10 mg/day for free nicotinic acid is not applicable during pregnancy or lactation because of inadequate data relating to this critical life stage. Nicotinamide Nicotinamide does not produce the flushing response that has been used as the basis for the upper level for nicotinic acid. There has been only one reported case of hepatotoxicity in a patient receiving high-dose nicotinamide (however, nicotinamide has not been subject to extensive clinical trials [at 3 g per day or more] for use as a hypolipidaemic agent). No significant adverse effects have been reported in trials on the possible benefits of nicotinamide in patients with or at risk of diabetes, which have used doses up to the equivalent of 3 g per day, for periods up to 3 years. This value represents the lowest reported dose in a number of recent trials of high quality, many of which used sensitive markers of hepatic function and glucose homeostasis, and included a range of age groups, with some subjects treated with up to 50 mg/kg bw/day. An uncertainty factor of 2 has been used to allow for the fact that adults may eliminate nicotinamide more slowly than the study groups, many of which were children, and that data for children would not reflect the full extent of intersubject variability that could occur in an older population. This form does not produce flushing and seems to be of low toxicity compared with nicotinic acid.
Four of the 5 animals in the high dose group (200 mg/kg/day) showed ataxia and loss of balance after 45 days of treatment allergy shots dc order periactin online from canada, whilst the other animal showed clinical signs after 75 days: histological examination of tissues at termination showed bilateral loss of myelin and axons in the dorsal funiculi and loss of fibres in the dorsal roots allergy shots for yeast order periactin 4mg free shipping. Animals in the low dose group (50 mg/kg/day) showed no clinical signs allergy symptoms 2014 purchase line periactin, but histological examination revealed loss of myelin in the dorsal nerve roots in all five dogs allergy testing long island discount periactin 4mg fast delivery. Hoover and Carlton (1981a) reported that all dogs (5 male and 5 female) treated with 150 mg pyridoxine/kg/day for 100-112 days developed neurologic disease characterised by ataxia involving predominantly the hind limbs at first, but with time, the fore limbs were also affected. Hind limb flexor reflexes were mildly reduced in two dogs and pain perception (pinprick) was mildly reduced in four. However, all dogs remained alert and cranial nerve and ophthalmologic tests were normal. Comparison of the data of Phillips et al (1978), Hoover and Carlton (1981a) and Krinke et al (1980) indicates a possible inverse relationship between dose and time to effect. Studies in humans Interpretation of the data from investigations in humans and case reports (summarised above) indicate that adverse neurological effects are detected after very high doses (>500 mg/day which is equivalent to about 8 mg/kg/day). Because of the severity of the adverse effects, there have been few studies designed to define the dose-response relationship in humans. The most important clinical studies are summarised in Table 3 and discussed below. Clinical studies that reported neurological effects Berger et al (1992) studied only extremely high doses, and did not define a non-effect level. Either 1 or 3 g of pyridoxine was given daily to 5 healthy volunteers until signs of either clinical or laboratory abnormality were present. The duration of treatments in the 5 subjects associated with the onset of symptoms was >14, 7, 4. The data demonstrated a clear inverse relationship between the dosage and the duration of consumption prior to the onset of symptoms. The author stated that his own studies did not find neurological effects in 70 patients at doses of 100 or 150 mg/day for up to 5 years. However there is a discrepancy between this statement and the publications (Del Tredici et al (1985) and Bernstein and Lobitz (1988)) cited to support this conclusion, in relation to the numbers of patients, the dosage (150-300 mg/day) and most importantly the duration (mostly less than 6 months). Bernstein (1990) hypothesised that there may be predisposing factors which may make some individuals more sensitive. The development of peripheral neuropathy has been reported in patients taking lower doses. A short report (Dalton, 1985) stated that 40% of women who had been taking vitamin supplements for premenstrual tension and who had plasma vitamin B6 levels above normal (3-18 ng/ml), developed various clinical signs consistent with peripheral neuropathy. The signs included shooting and tingling pains, paraesthesia of limbs, clumsiness, ataxia or peri-oral numbness. The vitamin B6 intake of these women ranged from 50-300 mg per day and involved a variety of multivitamin preparations. Two months after stopping all supplements, 27 of the women were reassessed and all showed improvement. In a subsequent study (Dalton and Dalton, 1987), vitamin B6 intake and clinical signs were monitored in women attending a private clinic specialising in the treatment of premenstrual tension. Of 172 women who were found to have elevated vitamin B6 serum levels (>18 ng/ml), 103 (60%) complained of neurological symptoms, while the other 69 had no symptoms. The neurological symptoms included paraesthesia, bone pains, hyperaesthesia, muscle weakness, fasciculation and numbness. Three months after stopping vitamin B6 intake, 55% of the women reported partial or complete recovery from the neurological symptoms and at 6 months, all reported complete recovery and the areas of hyperaesthesia and numbness noted at the initial examination had disappeared. Seven women who had inadvertently not stopped vitamin B6 intake all reported a continuation of their symptoms. Three women had subnormal serum B6 levels on cessation of supplement intake, and restarted B6 at a daily dose of 50 mg; however, symptoms returned and they stopped the supplement intake. In one case, a woman who had taken 75 mg of B6 daily together with multivitamins, zinc and magnesium, for 2 years, and had serum B6 level of >34 ng/ml, complained of paraesthesia of the hands, electric shock pains in her head, numbness of the finger tips and itching between her shoulder blades. Examination revealed patchy areas of hypersensitivity on her back and lower limbs, especially her shins. However, on restarting B6 intake at 50 mg per day for 3 months, the same neurological symptoms returned. The appearance of neurological symptoms at lower doses appears to be related to duration of intake which is compatible with the conclusion from Table 1. This study has been severely criticised because of its design; all subjects received vitamin B6 and the comparisons were between those who did, and those who did not report adverse effects. The only evidence for cause and effect relates to the consequence of stopping or not stopping intake, and correlations with duration of intake. Individuals, who had reported adverse effects, had been taking B6 for longer than those who did not have symptoms, and a higher proportion (70% compared with 55%) had serum B6 levels >34 ng/ml. Clinical studies on pyridoxine in relation to neurological effects (see Table 2 for individual/anecdotal evidence) Duration Dosage Authors Subjects Number of Findings Conclusions (mg/day) treatment Adverse Too few subjects to Baker and Elderly 6 225 up to 1 year effects not provide useful data; Frank (1984) reported full data not published All subjects developed abnormal Clear evidence of measurements adverse effects at Berger et al Adults 5 1000-3000 up to 7 of vibration high doses with an (1992) months and/or thermal inverse relationship thresholds; 4 between dose and subjects deve symptom-free duration loped clinical symptoms Diabetic No changes in Limited duration Bernstein and patients with up to 6 motor conduc and high drop-out rate 16 150 Lobitz (1988) pre-existing months tion velocity at (only 5 subjects studied neuropathies 5 months at 5 months) Shooting performance (a reection of tremor); Duration too Bonke and Men 18 60 (n = 8) 8 weeks signicant short to assess Nickel (1989) (marksmen) 600 (n = 10) improvement in neurological effects score over the 8 week period compared to placebo No neurological Only 7% of patients Patients with effects were treated for Brush (1988) premenstrual cohort 1 40-200 mostly less reported 3 or more years. Dalton and premenstrual 172 <50-<500 <6 months but greater There was no control Dalton (1987) syndrome >5 years duration group and the evidence (2. Clinical studies on pyridoxine in relation to neurological effects (see Table 2 for individual/anecdotal evidence) Duration Dosage Authors Subjects Number of Findings Conclusions (mg/day) treatment No changes in distal Patients with motor Duration too Del Tredici et al carpal tunnel 24 150 or 300 4 months latency or short to assess (1985) syndrome self-asses neurological effects sment que stionnaire the condition may be due to pyridoxine de Ellis et al Patients with No adverse ciency; typical treatment (1979) (and carpal tunnel 35 100-300 up to 12 neurologi schedule of 12 weeks studies cited); syndrome weeks cal effects (Ellis, 1987) is of too short Ellis (1987) reported duration to access neurological effects Patients with No assess Duration too Kerr (1977) premenstrual 70 40-100 2 months ment of side short to assess syndrome effects neurological effects No neurolo gical com Small group size but plications in very extended duration; Patients with 22 patients inuence of the or nerve Mitwalli et al hyperoxaluria 22 250-500 1-6 years conduction disease on (1984) (kidney abnorma pyridoxine handling, stones) requirements and lities in 7 patients neurological response are not known studied in detail Small group size but very No abnor extended duration; the malities of absence of effects at Patients with motor or doses equivalent to 10-90 Mpofu et al homocystei 17 200-500 10-24 years sensory mg/kg/day suggests that (1991) nuria nerve these patients may show conduction reduced responsiveness velocities to the neuronal adverse effects of pyridoxine Pauling (1984) Undened >5000 200 not given No details No details available; cites Hawkins patients cannot be assessed No asses Results from a survey Pullon et al Women 410 not described not described sments of of 1826 women; no (1989) possible data on tolerability neuropathy and side effects No effects Small number of subjects and very limited Tolis et al Women 9 200 or 400 2 months on growth duration of treatment; (1977) hormone or no assessment of prolactin neurological effects No diffe rence in Women with side effects Duration too Williams et al premenstrual 204 (out 100 3 months between short to access (1985) syndrome of 434) treatments neurological effects and placebo groups Data asses sment for A systematic review of published and Women with reports of unpublished Wyatt et al premenstrual 526 (out 50-600 up to 4 side effects; randomised (1999) syndrome of 910) months 1 reported placebo controlled case of trials; all studies of neurological inadequate duration side effects 37 europa. This cohort appears to have been the same as that described by Brush et al (1988), and mentioned by Brush and Perry (1985) in their letter concerning the Dalton study. Neuropathy was not reported in the group of 630 women who received between 80 and 200 mg pyridoxine daily for premenstrual syndrome (Brush, 1988; Brush and Perry, 1985). This same cohort of patients was described by Brush et al (1988), and it is clear that the data are limited by the duration of the study because 80% of the subjects were treated for 12 months or less, and 93% for 24 months or less: neurological assessment was not performed and the tolerability of the treatment was assessed by the patients. Interpretation of the various studies is complicated by differences in the duration of treatment. A large number of the studies are in women taking high doses of vitamin B6 for premenstrual syndrome. Adverse effects were not reported in a group of 6 elderly individuals given 225 mg pyridoxine per day for one year (Baker and Frank, 1984). In a letter to the New England Journal of Medicine, Pauling (1984) stated that a similar dose (200 mg pyridoxine daily) had been given to more than 5000 subjects without reports of side-effects (but these data cannot be evaluated because the duration of intake is not known and the cited reference (Hawkins, 1973) is not available in peer-reviewed literature). A cohort of 434 patients with premenstrual syndrome was divided into two groups: one group received 100 mg pyridoxine per day and the other group were given a placebo. The patients were allowed to increase the dose to 200 mg/day if they considered they were receiving no benefit from the initial treatment (Williams et al, 1985). Patients were studied over 3 menstrual cycles only and therefore the duration of intake and dose were inadequate to allow assessment of any possible neurotoxicity associated with pyridoxine. Two preliminary reports (Kerr, 1977; Day, 1979) studied the potential value of pyridoxine in the treatment of premenstrual syndrome. Neither study was of sufficient duration (2 months and 7 months respectively) or assessed symptoms sufficiently rigorously to be of value in relation to establishing possible adverse effects of vitamin B6. A large group of women with premenstrual symptoms (n = 1826) was studied by Pullon et al (1989) largely in relation to the syndrome and its management, but this large study provided no data on possible pyridoxine neuropathy. A recent systematic review of studies on the use of vitamin B6 in premenstural syndrome (Wyatt et al, 1999) showed an improvement compared to placebo. Adverse effects were limited to one case of neuropathy that could be attributed to pyridoxine. Dosages ranged from 50-600 mg/day, but the studies were too short in duration (usually 2-4 months) to exclude the possibility of neuropathy after prolonged intake at such intakes. A small study in patients with carpal tunnel syndrome by Del Tredici et al (1985) described the treatment of 16 patients with 150 mg vitamin B6 for 4 months and 8 patients with 300 mg B6 for 4 months. No details of neurological assessment were given and the duration of the study limits its value for assessing adverse effects after long-term treatment. Order 4 mg periactin with visa. Psoriasis - causes symptoms diagnosis treatment pathology. |
