Methods: Ninety consecutive patients with untreated NCC underwent a cognitive assessment (Mini-mental State Examination, Neurobehavioral Cognitive Status Examination, and IQCODE) and were classified as having or not having dementia according to DSM-IV criteria. Imaging and cerebrospinal fluid examination data were recorded. The cognitive measures were repeated six months after treatment with albendazole and steroids. Results: At the initial evaluation 15.5% (n = 14) of the patients were classified as having dementia. Dementia was associated with older age, lower education level, increased number of parasitic lesions in the brain (mostly in the frontal, temporal, and parietal lobes). After six months, 21.5% of the patients from the dementia group continued to have a full dementia disorder and 78.5% no longer fulfilled the DSM-IV criteria for dementia, although some of these patients still showed mild cognitive decline. Conclusions: The results of this study suggest that dementia occurs frequently in patients with untreated NCC, and it is reversible in most cases.


Neurocysticercosis (NCC) is an infection of the central nervous system (CNS) caused by the metacestode larval form of the parasite Taenia sp. Many factors can contribute to the endemic nature of cysticercosis. The inflammatory process that occurs in the tissue surrounding the parasite and/or distal from it can result from several associated mechanisms and may be disproportionate with the number of cysts. This discrepancy may lead to difficulty with the proper diagnosis in people from low endemic regions or regions that lack laboratory resources. In the CNS, the cysticerci have two basic forms, isolated cysts (Cysticercus cellulosae=CC) and racemose cysts (Cysticercus racemosus=CR), and may be meningeal, parenchymal, or ventricular or have a mixed location. The clinical manifestations are based on two fundamental syndromes that may occur in isolation or be associated: epilepsy and intracranial hypertension. They may be asymptomatic, symptomatic or fatal; have an acute, sub-acute or chronic picture; or may be in remission or exacerbated. The cerebrospinal fluid (CSF) may be normal, even in patients with viable cysticerci, until the patients begin to exhibit the classical syndrome of NCC in the CSF, or show changes in one or more routine analysed parameters. Computed tomography (CT) and magnetic resonance imaging (MRI) have allowed non-invasive diagnoses, but can lead to false negatives. Treatment is a highly controversial issue and is characterised by individualised therapy sessions. Two drugs are commonly used, praziquantel (PZQ) and albendazole (ABZ). The choice of anti-inflammatory drugs includes steroids and dextrochlorpheniramine (DCP). Hydrocephalus is a common secondary effect of NCC. Surgical cases of hydrocephalus must be submitted to ventricle-peritoneal shunt (VPS) immediately before cysticidal treatment, and surgical extirpation of the cyst may lead to an absence of the surrounding inflammatory process. The progression of NCC may be simple or complicated, have remission with or without treatment and may exhibit symptoms that can disappear for long periods of time or persist until death. Unknown, neglected and controversial aspects of NCC, such as the impaired fourth ventricle syndrome, the presence of chronic brain oedema and psychic complaints, in addition to the lack of detectable glucose in the CSF and re-infection are discussed.


Neurocysticercosis (NCC) is the most frequent parasitic disease of the human brain. Modern imaging studies, CT and MRI, have defined the diagnosis and characterization of the disease. Through these studies the therapeutic approach for each case may be individualized with the aid of antihelmintics, steroids, symptomatic medicines, or surgery. The use of one or various therapeutic measures largely depends on the peculiar combination of number, location, and biological stage of lesions as well as the degree of inflammatory response to the parasites. Although there is not a typical clinical picture of NCC, epilepsy is the most frequent manifestation of parenchymal NCC, whereas hydrocephalus is the most frequent manifestation of meningeal NCC. Eradication of cysticercosis is an attainable goal by public education and sanitary improvement in endemic areas.


OBJECTIVES: Neurocysticercosis (NCYST) is the most frequent CNS parasitic disease worldwide, affecting more than 50 million people. However, some of its clinical findings, such as cognitive impairment and dementia, remain poorly characterized, with no controlled studies conducted so far. We investigated the frequency and the clinical profile of cognitive impairment and dementia in a sample of patients with NCYST in comparison with cognitively healthy controls (HC) and patients with cryptogenic epilepsy (CE). METHODS: Forty treatment-naive patients with NCYST, aged 39.25 +/- 10.50 years and fulfilling absolute criteria for definitive active NCYST on MRI, were submitted to a comprehensive cognitive and functional evaluation and were compared with 49 HC and 28 patients with CE of similar age, educational level, and seizure frequency. RESULTS: Patients with NCYST displayed significant impairment in executive functions, verbal and nonverbal memory, constructive praxis, and verbal fluency when compared with HC (p < 0.05). Dementia was diagnosed in 12.5% patients with NCYST according to DSM-IV criteria. When compared with patients with CE, patients with NCYST presented altered working and episodic verbal memory, executive functions, naming, verbal fluency, constructive praxis, and visual-spatial orientation. No correlation emerged between cognitive scores and number, localization, or type of NCYST lesions on MRI. CONCLUSIONS: Cognitive impairment was ubiquitous in this sample of patients with active neurocysticercosis (NCYST). Antiepileptic drug use and seizure frequency could not account for these features. Dementia was present in a significant proportion of patients. These data broaden our knowledge on the clinical presentations of NCYST and its impact in world public health.


Four cases of suggestive inflammatory aneurysms in patients with neurocysticercosis have been described. We report a case of a 49-year-old woman who presented with subarachnoid haemorrhage from a right middle cerebral artery bifurcation aneurysm and had a casual relationship with neurocysticercosis. At surgery, a viable cysticercus without signs of inflammation or thickened leptomeninges was found in the distal position of the aneurysm. Postoperatively, the patient received albendazole and dextrochlorpheniramine. In the subsequent three years, the patient was asymptomatic and took drugs to prevent convulsion and arterial hypertension. The relationship between NCC and the presence of cerebral aneurysm is discussed.


OBJECTIVE: To determine the frequency and features of psychiatric morbidity in a cross section of 38 outpatients with neurocysticercosis. METHODS: Diagnosis of neurocysticercosis was established by CT, MRI, and CSF analysis. Psychiatric diagnoses were made by using the present state examination and the schedule for affective disorders and schizophrenia-lifetime version; cognitive state was assessed by mini mental state examination and Strub and Black's mental status examination. RESULTS: Signs of psychiatric disease and cognitive decline were found in 65.8 and 87.5% of the cases respectively. Depression was the most frequent psychiatric diagnosis (52.6%) and 14.2% of the patients were psychotic. Active disease and intracranial hypertension were associated with higher psychiatric morbidity, and previous history of mood disorders was strongly related to current depression. Other variables, such as number and type of brain lesions, severity of neuropsychological deficits, epilepsy, and use of steroids did not correlate with mental disturbances in this sample. CONCLUSIONS: Psychiatric abnormalities, particularly depression syndromes, are frequent in patients with neurocysticercosis. Although regarded as a rare cause of dementia, mild cognitive impairment may be a much more prevalent neuropsychological feature of patients with neurocysticercosis. The extent to which organic mechanisms related to brain lesions may underlie the mental changes is yet unclear, although the similar sex distribution of patients with and without depression, as well as the above mentioned correlations, provide further evidence of the part played by organic factors in the cause of these syndromes.


OBJECTIVE: Review of human cysticercosis in Canada, to estimate the magnitude of the disease and to describe the pattern of disease expression in this country. METHODS: MEDLINE and manual search of case reports and case series of patients with cysticercosis diagnosed in Canada. ed data included year of diagnosis, citizenship status, clinical manifestations, and form of cysticercosis. FINDINGS: A total of 21 articles reporting 60 patients were found. Forty (67%) of these patients were diagnosed in the past two decades. Most cases came from Ontario (n=43) and Quebec (n=14). Immigrants accounted for 96% of the 28 cases in whom citizenship information was available. Neurocysticercosis was observed in 55 patients, and isolated compromise of striated muscles in the remaining five. Seizures was the primary or sole manifestation of the disease in 72% of patients, and most of them had parenchymal brain cysticerci (either viable cysts or calcifications). Two of seven patients were positive for Taenia eggs. In no case were household contacts of the patients investigated for taeniasis. CONCLUSIONS: An increasing number of patients with cysticercosis have been reported from Canada in the past two decades, suggesting that the prevalence of this parasitic disease may be on the rise. While most cases occur in immigrants, it is possible that at least some of these patients had acquired the disease in Canada.


Background Multiple Myeloma (MM) is a B cell neoplasm causing lytic or osteopenic bone abnormalities. Whole body skeletal survey (WBSS), Magnetic resonance (MR) and 18F-FDG PET/CT are imaging techniques routinely used for the evaluation of bone involvement in MM patients. Aim As MM bone lesions may present low 18F-FDG uptake; the aim of this study was to assess the possible added value and limitations of 11C-Choline to that of 18F-FDG PET/CT in patients affected with MM. Methods Ten patients affected with MM underwent a standard 11C-Choline PET/CT and an 18F-FDG PET/CT within one week. The results of the two scans were compared in terms of number, sites and SUVmax of lesions. Results Four patients (40%) had a negative concordant 11C-Choline and 18F-FDG PET/CT scans. Two patients (20%) had a positive 11C-Choline and 18F-FDG PET/CT scans that identified the same number and sites of bone lesions. The remaining four patients (40%) had a positive 11C-Choline and 18F-FDG PET/CT scan, but the two exams identified different number of lesions. Choline showed a mean SUVmax of 5 while FDG showed a mean SUVmax of 3.8 (P = 0.042). Overall, 11C-Choline PET/CT scans detected 37 bone lesions and 18F-FDG PET/CT scans detected 22 bone lesions but the difference was not significant (P = 0.8). Conclusion According to these preliminary data, 11C-Choline PET/CT appears to be more sensitive than 18F-FDG PET/CT for the detection of bony myelomatous lesions. If these data are confirmed in larger series of patients, 11C-Choline may be considered a more appropriate functional imaging in association with MRI for MM bone staging.


Background: A Step I diet with lean beef compared with lean white meat both decrease LDL cholesterol. To our knowledge, no studies have evaluated a low–saturated fatty acid (SFA) (<7% calories) diet that contains lean beef. Objective: We studied the effect on LDL cholesterol of cholesterol-lowering diets with varying amounts of lean beef [ie, Dietary Approaches to Stop Hypertension (DASH): 28 g beef/d; Beef in an Optimal Lean Diet (BOLD): 113 g beef/d; and Beef in an Optimal Lean Diet plus additional protein (BOLD+): 153 g beef/d] compared with that of a healthy American diet (HAD). Design: Thirty-six hypercholesterolemic participants (with LDL-cholesterol concentrations >2.8 mmol/L) were randomly assigned to consume each of the 4 diets (HAD: 33% total fat, 12% SFA, 17% protein, and 20 g beef/d), DASH (27% total fat, 6% SFA, 18% protein, and 28 g beef/d), BOLD (28% total fat, 6% SFA, 19% protein, and 113 g beef/d), and BOLD+ (28% total fat, 6% SFA, 27% protein, and 153 g beef/d) for 5 wk. Results: There was a decrease in total cholesterol (TC) and LDL-cholesterol concentrations (P < 0.05) after consumption of the DASH (−0.49 ± 0.11 and −0.37 ± 0.09 mmol/L, respectively), BOLD (−0.48 ± 0.10 and −0.35 ± 0.9 mmol/L, respectively), and BOLD+ (−0.50 ± 0.10 and −0.345 ± 0.09 mmol/L, respectively) diets compared with after consumption of the HAD (−0.22 ± 0.10 and −0.14 ± 0.10 mmol/L, respectively). Apolipoprotein A-I, C-III, and C-III bound to apolipoprotein A1 particles decreased after BOLD and BOLD+ diets compared with after the HAD, and there was a greater decrease in apolipoprotein B after consumption of the BOLD+ diet than after consumption of the HAD (P < 0.05 for both). LDL cholesterol and TC decreased after consumption of the DASH, BOLD, and BOLD+ diets when the baseline C-reactive protein (CRP) concentration was <1 mg/L; LDL cholesterol and TC decreased when baseline CRP concentration was >1 mg/L with the BOLD and BOLD+ diets. Conclusions: Low-SFA, heart-healthy dietary patterns that contain lean beef elicit favorable effects on cardiovascular disease (CVD) lipid and lipoprotein risk factors that are comparable to those elicited by a DASH dietary pattern. These results, in conjunction with the beneficial effects on apolipoprotein CVD risk factors after consumption of the BOLD and BOLD+ diets, which were greater with the BOLD+ diet, provide support for including lean beef in a heart-healthy dietary pattern. This trial was registered at clinicaltrials.gov as NCT00937898.


BACKGROUND: Despite its high content of saturated fatty acids, cheese does not seem to increase plasma total and LDL-cholesterol concentrations when compared with an equivalent intake of fat from butter. This effect may be due to the high calcium content of cheese, which results in a higher excretion of fecal fat. OBJECTIVES: The objective was to compare the effects of diets of equal fat content rich in either hard cheese or butter or a habitual diet on blood pressure and fasting serum blood lipids, C-reactive protein, glucose, and insulin. We also examined whether fecal fat excretion differs with the consumption of cheese or butter. DESIGN: The study was a randomized dietary intervention consisting of two 6-wk crossover periods and a 14-d run-in period during which the subjects consumed their habitual diet. The study included 49 men and women who replaced part of their habitual dietary fat intake with 13% of energy from cheese or butter. RESULTS: After 6 wk, the cheese intervention resulted in lower serum total, LDL-, and HDL-cholesterol concentrations and higher glucose concentrations than did the butter intervention. Cheese intake did not increase serum total or LDL-cholesterol concentrations compared with the run-in period, during which total fat and saturated fat intakes were lower. Fecal fat excretion did not differ between the cheese and butter periods. CONCLUSION: Cheese lowers LDL cholesterol when compared with butter intake of equal fat content and does not increase LDL cholesterol compared with a habitual diet. This trial is registered at clinicaltrials.gov as NCT01140165.


It has been well established that complex mixtures of phytochemicals in fruits and vegetables can be beneficial for human health. Moreover, it is becoming increasingly apparent that phytochemicals can influence the pharmacological activity of drugs by modifying their absorption characteristics through interactions with drug transporters as well as drug-metabolizing enzyme systems. Such effects are more likely to occur in the intestine and liver, where high concentrations of phytochemicals may occur. Alterations in cytochrome P450 and other enzyme activities may influence the fate of drugs subject to extensive first-pass metabolism. Although numerous studies of nutrient-drug interactions have been published and systematic reviews and meta-analyses of these studies are available, no generalizations on the effect of nutrient-drug interactions on drug bioavailability are currently available. Several publications have highlighted the unintended consequences of the combined use of nutrients and drugs. Many phytochemicals have been shown to have pharmacokinetic interactions with drugs. The present review is limited to commonly consumed fruits and vegetables with significant beneficial effects as nutrients and components in folk medicine. Here, we discuss the phytochemistry and pharmacokinetic interactions of the following fruit and vegetables: grapefruit, orange, tangerine, grapes, cranberry, pomegranate, mango, guava, black raspberry, black mulberry, apple, broccoli, cauliflower, watercress, spinach, tomato, carrot, and avocado. We conclude that our knowledge of the potential risk of nutrient-drug interactions is still limited. Therefore, efforts to elucidate potential risks resulting from food-drug interactions should be intensified in order to prevent undesired and harmful clinical consequences. © 2011 Institute of Food Technologists®


In vitro and in vivo studies have shown that cytochrome P450 3A4 (CYP3A4) is involved in the metabolism of oestrogens. There is evidence that grapefruit, an inhibitor of CYP3A4, increases plasma oestrogen concentrations. Since it is well established that oestrogen is associated with breast cancer risk, it is plausible that regular intake of grapefruit would increase a woman's risk of breast cancer. We investigated the association of grapefruit intake with breast cancer risk in the Hawaii–Los Angeles Multiethnic Cohort Study, a prospective cohort that includes over 50 000 postmenopausal women from five racial/ethnic groups. A total of 1657 incident breast cancer cases were available for analysis. Grapefruit intake was significantly associated with an increased risk of breast cancer (relative risk=1.30, 95% confidence interval 1.06–1.58) for subjects in the highest category of intake, that is, one-quarter grapefruit or more per day, compared to non-consumers (Ptrend=0.015). An increased risk of similar magnitude was seen in users of oestrogen therapy, users of oestrogen+progestin therapy, and among never users of hormone therapy. Grapefruit intake may increase the risk of breast cancer among postmenopausal women.


Background Reducing dietary energy density has proven to be an effective strategy to reduce energy intakes and promote weight control. This effect appears most robust when a low energy dense preload is consumed before meals. Yet, much discussion continues regarding the optimal form of a preload. The purpose of the present study was to compare effects of a solid (grapefruit), liquid (grapefruit juice) and water preload consumed prior to breakfast, lunch and dinner in the context of caloric restriction. Methods Eighty-five obese adults (BMI 30-39.9) were randomly assigned to (127 g) grapefruit (GF), grapefruit juice (GFJ) or water preload for 12 weeks after completing a 2-week caloric restriction phase. Preloads were matched for weight, calories, water content, and energy density. Weekly measures included blood pressure, weight, anthropometry and 24-hour dietary intakes. Resting energy expenditure, body composition, physical performance and cardiometabolic risk biomarkers were assessed. Results The total amount (grams) of food consumed did not change over time. Yet, after preloads were combined with caloric restriction, average dietary energy density and total energy intakes decreased by 20-29% from baseline values. Subjects experienced 7.1% weight loss overall, with significant decreases in percentage body, trunk, android and gynoid fat, as well as waist circumferences (-4.5 cm). However, differences were not statistically significant among groups. Nevertheless, the amount and direction of change in serum HDL-cholesterol levels in GF (+6.2%) and GFJ (+8.2%) preload groups was significantly greater than water preload group (-3.7%). Conclusions These data indicate that incorporating consumption of a low energy dense dietary preload in a caloric restricted diet is a highly effective weight loss strategy. But, the form of the preload did not have differential effects on energy balance, weight loss or body composition. It is notable that subjects in GF and GFJ preload groups experienced significantly greater benefits in lipid profiles. Trial registration ClinicalTrials.gov NCT00581074


The contents of the bioactive compounds in red and blond grapefruits and their influence on humans suffering from hypertriglyceridemia were studied. It was found that red grapefruit has a higher content of bioactive compounds and a higher antioxidant potential than blond grapefruit, determined by oxygen radical scavenging capacity, 1,1-diphenyl-2-picrylhydrazyl, carotenoid bleaching, and Folin-Ciocalteu assays. Fifty-seven hyperlipidemic patients, ages 39-72 years, after coronary bypass surgery, recruited from the Institute's pool of volunteers, were randomly divided into three equal in number (19) groups: two experimental (red and blond groups) and one control group (CG). During 30 consecutive days of the investigation the diets of the patients of the red and blond dietary groups were daily supplemented with one equal in weight fresh red or blond grapefruit, respectively. Before and after this trial, serum lipid levels of all fractions and serum antioxidant activity were determined. It was found that serum lipid levels in patients of the red and blond groups versus the CG after treatment were decreased: (a) total cholesterol, 6.69 versus 7.92 mmol/L, 15.5%, and 7.32 versus 7.92 mmol/L, 7.6%, respectively; (b) low-density lipoprotein cholesterol, 5.01 versus 6.29 mmol/L, 20.3%, and 5.62 versus 6.29 mmol/L, 10.7%, respectively; (c) triglycerides, 1.69 versus 2.32 mmol/L, 17.2%, and 2.19 versus 2.32 mmol/L, 5.6%, respectively. No changes in the serum lipid levels in patients of the CG were found. In conclusion, fresh red grapefruit contains higher quantities of bioactive compounds and has significantly higher antioxidant potential than blond grapefruit. Diet supplemented with fresh red grapefruit positively influences serum lipid levels of all fractions, especially serum triglycerides and also serum antioxidant activity. The addition of fresh red grapefruit to generally accepted diets could be beneficial for hyperlipidemic, especially hypertriglyceridemic, patients suffering from coronary atherosclerosis.


To study the effects of grapefruit and grapefruit products on body weight and metabolic syndrome, 91 obese patients were randomized to either placebo capsules and 7 ounces (207 mL) of apple juice, grapefruit capsules with 7 ounces (207 mL) of apple juice, 8 ounces (237 mL) of grapefruit juice with placebo capsule, or half of a fresh grapefruit with a placebo capsule three times a day before each meal. Metabolic syndrome parameters were measured at the beginning and end of 12 weeks. After 12 weeks, the fresh grapefruit group had lost 1.6 kg, the grapefruit juice group had lost 1.5 kg, the grapefruit capsule group had lost 1.1 kg, and the placebo group had lost 0.3 kg. The fresh grapefruit group lost significantly more weight than the placebo group (P < .05). A secondary analysis of those with the metabolic syndrome in the four treatment groups demonstrated a significantly greater weight loss in the grapefruit, grapefruit capsule, and grapefruit juice groups compared with placebo (P < .02). There was also a significant reduction in 2-hour post-glucose insulin level in the grapefruit group compared with placebo. Half of a fresh grapefruit eaten before meals was associated with significant weight loss. In metabolic syndrome patients the effect was also seen with grapefruit products. Insulin resistance was improved with fresh grapefruit. Although the mechanism of this weight loss is unknown it would appear reasonable to include grapefruit in a weight reduction diet.


This study evaluated the effect of adding fruit or oats to the diet of free-living women on energy consumption and body weight. Fruit and oat cookies had the same amount of fiber and total calories ( approximately 200 kcal), but differed in energy density. We analyzed data from a clinical trial conducted in a primary care unit in Rio de Janeiro, Brazil. Forty-nine women, ages ranging from 30 to 50 years, with body mass index (BMI)>25 kg/m2, were randomly chosen to add three apples (0.63 kcal/g energy density) or three pears (0.64 kcal/g energy density) or three oat cookies (3.7 kcal/g energy density) to their usual diet for 10 weeks. Fiber composition was similar ( approximately 6g). Statistical analysis of the repeated measures of dietary composition and body weight were analyzed using mixed model procedures. Results showed a significant decrease in the energy density during the follow-up (-1.23 kcal/g, p<0.04, and -1.29 kcal/g, p<0.05) for apples and pears, respectively, compared to the oat group. The energy intake also decreased significantly (-25.05 and -19.66 kcal/day) for the apple and pear group, respectively, but showed a small increase (+0.93) for the oat group. Apples and pears were also associated (p<0.001) with weight reduction (-0.93 kg for the apple and -0.84 for the pear group), whereas weight was unchanged (+0.21; p=0.35) in the oat group. Results suggest that energy densities of fruits, independent of their fiber amount can reduce energy consumption and body weight over time.


The average American diet, which is high in protein and low in fruits and vegetables, generates a large amount of acid, mainly as sulfates and phosphates. The kidneys respond to this dietary acid challenge with net acid excretion, as well as ammonium and titratable acid excretion. Concurrently, the skeleton supplies buffer by active resorption of bone. Indeed, calciuria is directly related to net acid excretion. Different food proteins differ greatly in their potential acid load, and therefore in their acidogenic effect. A diet high in acid-ash proteins causes excessive calcium loss because of its acidogenic content. The addition of exogenous buffers, as chemical salts or as fruits and vegetables, to a high protein diet results in a less acid urine, a reduction in net acid excretion, reduced ammonium and titratable acid excretion, and decreased calciuria. Bone resorption may be halted, and bone accretion may actually occur. Alkali buffers, whether chemical salts or dietary fruits and vegetables high in potassium, reverse acid-induced obligatory urinary calcium loss. We conclude that excessive dietary protein from foods with high potential renal acid load adversely affects bone, unless buffered by the consumption of alkali-rich foods or supplements.


Increasing dietary protein results in an increase in urinary calcium. Despite over 80 y of research, the source of the additional urinary calcium remains unclear. Because most calcium balance studies found little effect of dietary protein on intestinal calcium absorption, it was assumed that the skeleton was the source of the calcium. The hypothesis was that the high endogenous acid load generated by a protein-rich diet would increase bone resorption and skeletal fracture. However, there are no definitive nutrition intervention studies that show a detrimental effect of a high protein diet on the skeleton and the hypothesis remains unproven. Recent studies from our laboratory demonstrate that dietary protein affects intestinal calcium absorption. We conducted a series of short-term nutrition intervention trials in healthy adults where dietary protein was adjusted to either low, medium or high. The highest protein diet resulted in hypercalciuria with no change in serum parathyroid hormone. Surprisingly, within 4 d, the low protein diet induced secondary hyperparathyroidism that persisted for 2 wk. The secondary hyperparathyroidism induced by the low protein diet was attributed to a reduction in intestinal calcium absorption (as assessed by dual stable calcium isotopes). The long-term consequences of these low protein-induced changes in calcium metabolism are not known, but they could be detrimental to skeletal health. Several recent epidemiological studies demonstrate reduced bone density and increased rates of bone loss in individuals habitually consuming low protein diets. Therefore, studies are needed to determine whether low protein intakes directly affect rates of bone resorption, bone formation or both.


To investigate whether systemic acid-base equilibrium changes with aging in normal adult humans, we reviewed published articles reporting the acid-base composition of arterial, arterialized venous, or capillary blood in age-identified healthy subjects. We extracted or calculated blood hydrogen ion concentration ([H+]), plasma bicarbonate concentration ([HCO3(-)]), blood PCO2, and age, and computed a total of 61 age-group means, distributed among eight 10-year intervals from age 20 to 100 years. Using linear regression analysis, we found that with increasing age, there is a significant increase in the steady-state blood [H+] (p < .001), and reduction in steady-state plasma [HCO3(-)] (p < .001), indicative of a progressively worsening low-level metabolic acidosis. Blood PCO2 decreased with age (p < .05), in keeping with the expected respiratory adaptation to metabolic acidosis. Such age-related increasing metabolic acidosis may reflect in part the normal decline of renal function with increasing age. The role of age-related metabolic acidosis in the pathogenesis of the degenerative diseases of aging warrants consideration.


Background Maintaining muscle mass while aging is important to prevent falls and fractures. Metabolic acidosis promotes muscle wasting, and the net acid load from diets that are rich in net acid–producing protein and cereal grains relative to their content of net alkali–producing fruit and vegetables may therefore contribute to a reduction in lean tissue mass in older adults. Objective We aimed to determine whether there was an association of 24-h urinary potassium and an index of fruit and vegetable content of the diet with the percentage lean body mass (%LBM) or change in %LBM in older subjects. Design Subjects were 384 men and women ≥65 y old who participated in a 3-y trial comparing calcium and vitamin D with placebo. Potassium was measured in 24-h urine collections at baseline. The %LBM, defined as total body nonfat, nonbone tissue weight ÷ weight × 100, was measured by using dual-energy X-ray absorptiometry at baseline and at 3 y. Physical activity, height, and weight were assessed at baseline and at 3 y. Results At baseline, the mean urinary potassium excretion was 67.0 ± 21.1 mmol/d. Urinary potassium (mmol/d) was significantly positively associated with %LBM at baseline (β = 0.033, P = 0.006; adjusted for sex, weight, and nitrogen excretion) but not with 3-y change in %LBM. Over the 3-y study, %LBM increased by 2.6 ± 3.6%. Conclusion Higher intake of foods rich in potassium, such as fruit and vegetables, may favor the preservation of muscle mass in older men and women.


Background The finding reported in a previous paper - alkalization of urine facilitates uric acid excretion - is contradictory to what one might expect to occur: because food materials for the alkalization of urine contain fewer purine bodies than those for acidification, less uric acid in alkaline urine should have been excreted than in acid urine. To make clear what component of uric acid excretion mechanisms is responsible for this unexpected finding, we simultaneously collected data for the concentration of both creatinine and uric acid in serum as well as in urine, in order to calculate both uric acid and creatinine clearances. Methods Within the framework of the Japanese government’s health promotion program, we made recipes which consisted of protein-rich and less vegetable-fruit food materials for H + -load (acidic diet) and others composed of less protein and more vegetable-fruit rich food materials (alkaline diet). This is a crossover study within some limitations. Healthy female students, who had no medical problems at the regular physical examination provided by the university, were enrolled in this consecutive 5-day study for each test. From whole-day collected urine, total volume, pH, organic acid, creatinine, uric acid, titratable acid and all cations (Na+,K+,Ca2+,Mg2+,NH4+) and anions (Cl−,SO42−,PO4−) necessary for the estimation of acid–base balance were measured. In the early morning before breakfast of the 1st, 3rd and 5th experimental day, we sampled 5 mL of blood to estimate the creatinine and uric acid concentration in serum. Results and discussion Urine pH reached a steady state 3 days after switching from ordinary daily diets to specified regimens. The amount of acid generated ([SO42−] + organic acid − gut alkali)was linearly related with the excretion of acid (titratable acid + [NH4+] − [HCO3−]), indicating that H + in urine is generated by the metabolic degradation of food materials. Uric acid and excreted urine pH retained a linear relationship, as reported previously. Among the five factors which are associated with calculating clearances for both uric acid and creatinine, we identified a conspicuous difference between acidic and alkaline diets in the uric acid concentration in serum as well as in urine; uric acid in the serum was higher in the acidic group than in the alkaline group, while uric acid in the urine in the acidic group was lower than that in the alkaline group. These changes of uric acid in acidic urine and in serum were reflected in the reduction of its clearance. From these observations, it is considered that uric acid may be reabsorbed more actively in acidic urine than in alkaline urine. Conclusion We conclude that alkalization of urine by eating nutritionally well-designed alkaline -prone food is effective for removing uric acid from the body.


Context and Objective: Dietary intake of animal proteins is associated with an increase in urinary calcium and nephrolithiasis risk. We tested the hypothesis that the acid load imposed by dietary proteins causes this hypercalciuria. Design and Setting: In a short-term crossover metabolic study, an alkali salt was provided with a high-protein diet (HPD) to neutralize the acid load imparted by dietary proteins. Participants and Interventions: Eleven healthy volunteers were evaluated at the end of each of four phases while consuming metabolic diets with fixed calcium and sodium content. Phases 1 and 3 consisted of a control diet (CD). Phases 2 and 4 consisted of a eucaloric HPD (60 g/d animal proteins added to CD). Along with HPD in phases 2 and 4, subjects ingested 30 mEq twice daily of either potassium citrate (KCitrate, alkaline salt) or potassium chloride (KCl, control neutral salt). Results: KCitrate completely neutralized the acid load imparted by HPD (based on changes in urine pH and net acid excretion) and increased urinary citrate. Urinary calcium increased during both HPD phases compared with CD but was not significantly different between the HPD + KCl and HPD + KCitrate phases (182 ± 85 vs. 170 ± 85 mg/d; P = 0.28). Increased urinary saturation with respect to calcium oxalate and uric acid with HPD was abrogated by KCitrate. Conclusions: This study suggests that, at least in the short-term, mechanism(s) other than acid load account for hypercalciuria induced by HPD. The beneficial effect of KCitrate on nephrolithiasis risk with HPD is through correction of declines in urine pH and citrate.


Although high-protein diets induce hypercalciuria in humans, the source of the additional urinary calcium remains unclear. One hypothesis is that the high endogenous acid load of a high-protein diet is partially buffered by bone, leading to increased skeletal resorption and hypercalciuria. We used dual stable calcium isotopes to quantify the effect of a high-protein diet on calcium kinetics in women. The study consisted of 2 wk of a lead-in, well-balanced diet followed by 10 d of an experimental diet containing either moderate (1.0 g/kg) or high (2.1 g/kg) protein. Thirteen healthy women received both levels of protein in random order. Intestinal calcium absorption increased during the high-protein diet in comparison with the moderate (26.2 +/- 1.9% vs. 18.5 +/- 1.6%, P < 0.0001, mean +/- sem) as did urinary calcium (5.23 +/- 0.37 vs. 3.57 +/- 0.35 mmol/d, P < 0.0001, mean +/- sem). The high-protein diet caused a significant reduction in the fraction of urinary calcium of bone origin and a nonsignificant trend toward a reduction in the rate of bone turnover. There were no protein-induced effects on net bone balance. These data directly demonstrate that, at least in the short term, high-protein diets are not detrimental to bone.


A precise understanding of the role of dietary protein in bone health has been evasive despite decades of research. It is known that a dietary acid load is harmful to bone, and sulfur-containing amino acids are metabolized to provide such an acid load. It is also known that protein elevates urine calcium loss. However, recent clinical studies and a meta-analysis have indicated either no effect or a modest benefit associated with higher protein intakes. These contradictory considerations may be explained by the existence of a two-faced relationship between protein and bone, with simultaneous positive and negative pathways. In opposition to the negative effects of dietary acid load, protein may exert positive effects related to improving calcium absorption, increasing insulin-like growth factor 1, or improving lean body mass, which, in turn, improves bone strength. Putative mechanisms behind these pathways are reviewed here, and some limitations in the historical literature as well as suggested measures to counter these in the future are identified. When positive and negative pathways are considered in tandem, protein may offer modest benefits to bone in the presence of adequate dietary calcium and acid-neutralizing fruits and vegetables. © 2011 International Life Sciences Institute.


High-protein (HP) diets exert a hypercalciuric effect at constant levels of calcium intake, even though the effect may depend on the nature of the dietary protein. Lower urinary pH is also consistently observed for subjects consuming HP diets. The combination of these two effects was suspected to be associated with a dietary environment favorable for demineralization of the skeleton. However, increased calcium excretion due to HP diet does not seem to be linked to impaired calcium balance. In contrast, some data indicate that HP intakes induce an increase of intestinal calcium absorption. Moreover, no clinical data support the hypothesis of a detrimental effect of HP diet on bone health, except in a context of inadequate calcium supply. In addition, HP intake promotes bone growth and retards bone loss and low-protein diet is associated with higher risk of hip fractures. The increase of acid and calcium excretion due to HP diet is also accused of constituting a favorable environment for kidney stones and renal diseases. However, in healthy subjects, no damaging effect of HP diets on kidney has been found in either observational or interventional studies and it seems that HP diets might be deleterious only in patients with preexisting metabolic renal dysfunction. Thus, HP diet does not seem to lead to calcium bone loss, and the role of protein seems to be complex and probably dependent on other dietary factors and the presence of other nutrients in the diet.


OBJECTIVE: Diet affects urine pH and acid-base balance. Both excess acid/alkaline ash (EAA) and estimated net acid excretion (NAE) calculations have been used to estimate the effects of diet on urine pH. This study's goal was to determine if free-living vegans, lacto-ovo vegetarians, and omnivores have increasingly acidic urine, and to assess the ability of EAA and estimated NAE calculations to predict urine pH. DESIGN: This study used a cross-sectional design. SETTING AND PARTICIPANTS: This study assessed urine samples of 10 vegan, 16 lacto-ovo vegetarian, and 16 healthy omnivorous women in the Boston metropolitan area. Six 3-day food records from each dietary group were analyzed for EAA content and estimated NAE, and correlations with measured urine pH were calculated. RESULTS: The mean (+/- SD) urine pH was 6.15 +/- 0.40 for vegans, 5.90 +/- 0.36 for lacto-ovo vegetarians, and 5.74 +/- 0.21 for omnivores (analysis of variance, P = .013). Calculated EAA values were not significantly different among the three groups, whereas mean estimated NAE values were significantly different: 17.3 +/- 14.5 mEq/day for vegans, 31.3 +/- 8.5 mEq/day for lacto-ovo vegetarians, and 42.6 +/- 13.2 mEq/day for omnivores (analysis of variance, P = .01). The average deattenuated correlation between urine pH and EAA was 0.333; this value was -0.768 for estimated NAE and urine pH, with a regression equation of pH = 6.33 - 0.014 NAE (P = .02, r = -0.54). CONCLUSIONS: Habitual diet and estimated NAE calculations indicate the probable ranking of urine pH by dietary groups, and may be used to determine the likely acid-base status of an individual; EAA calculations were not predictive of urine pH.


This review looks at the role of an alkaline diet in health. Pubmed was searched looking for articles on pH, potential renal acid loads, bone health, muscle, growth hormone, back pain, vitamin D and chemotherapy. Many books written in the lay literature on the alkaline diet were also reviewed and evaluated in light of the published medical literature. There may be some value in considering an alkaline diet in reducing morbidity and mortality from chronic diseases and further studies are warranted in this area of medicine.


High dietary acid load (DAL) may be detrimental to bone mineral density (BMD). The objectives of the study were to: 1) evaluate the cross-sectional relation between DAL and BMD; 2) determine whether calcium intake modifies this association. Men (n=1218) and women (n=907) ≥60y were included from the National Health and Nutrition Examination Survey 2005–2008. Nutrient intake from 2–24h recalls was used to calculate net endogenous acid production (NEAP) and potential renal acid load (PRAL) (mEq/d). PRAL was calculated from dietary calcium (PRALdiet) and diet + supplemental calcium (PRALtotal). Tests for linear trend in adjusted mean BMD of the hip and lumbar spine were performed across energy adjusted NEAP and PRAL quartiles. Modification by calcium intake (dietary or total) above or below 800 mg/d was assessed by interaction terms. Overall, mean age was 69 ± 0.3y. Among women, there was no association between NEAP and BMD. PRALdiet was positively associated with proximal femur BMD (p trend=0.04). No associations were observed with PRALtotal at any BMD site (P-range: 0.38–0.82). Among men, no significant associations were observed of BMD with NEAP or PRAL. However, an interaction between PRALdiet and calcium intake was observed with proximal femur BMD (p=0.08). An inverse association between PRALdiet and proximal femur BMD was detected among men <800 mg/d dietary calcium (p=0.02); and no associations ≥800 mg/d (p=0.98). A significant interaction with PRALtotal was not observed. In conclusion, when supplemental calcium is considered, there is no association between DAL and BMD among adults. Men with low dietary calcium showed an inverse relation with PRAL at the proximal femur; in women no interaction was observed. This study highlights the importance of calcium intakes in counteracting the adverse effect of DAL on bone health. Further research should determine the relation between DAL and change in BMD with very low calcium intake.


Our objective in this study was to determine the effects of a high-protein and high-potential renal acid load (PRAL) diet on calcium (Ca) absorption and retention and markers of bone metabolism. In a randomized crossover design, 16 postmenopausal women consumed 2 diets: 1 with low protein and low PRAL (LPLP; total protein: 61 g/d; PRAL: -48 mEq/d) and 1 with high protein and high PRAL (HPHP; total protein: 118 g/d; PRAL: 33 mEq/d) for 7 wk each separated by a 1-wk break. Ca absorption was measured by whole body scintillation counting of radio-labeled (47)Ca. Compared with the LPLP diet, the HPHP diet increased participants' serum IGF-I concentrations (P < 0.0001), decreased serum intact PTH concentrations (P < 0.001), and increased fractional (47)Ca absorption (mean ± pooled SD: 22.3 vs. 26.5 ± 5.4%; P < 0.05) and urinary Ca excretion (156 vs. 203 ± 63 mg/d; P = 0.005). The net difference between the amount of Ca absorbed and excreted in urine did not differ between 2 diet periods (55 vs. 28 ± 51 mg/d). The dietary treatments did not affect other markers of bone metabolism. In summary, a diet high in protein and PRAL increases the fractional absorption of dietary Ca, which partially compensates for increased urinary Ca, in postmenopausal women. The increased IGF-I and decreased PTH concentrations in serum, with no change in biomarkers of bone resorption or formation, indicate a high-protein diet has no adverse effects on bone health.


A first objective of the present study was to estimate the acid-base balance of the food intake in vegetarians and non-vegetarians. A second objective was to evaluate if additional input of specific food items on the existing potential renal acid load (PRAL) list was necessary for the comparison of the two dietary patterns. Thirty vegetarians between the age of 18 and 30 years were matched for sex, age and BMI with 30 non-vegetarians. Based on the 3-days food diaries the acid-base status of the food intake was estimated using the PRAL method. Mean PRAL values as estimated with the standard table yielded an alkaline load of -5.4 +/- 14.4 mEq/d in the vegetarians compared to an acid load of 10.3 +/- 14.4 mEq/d in the nonvegetarians (p<0.001). Mean PRAL values as estimated with the extended table yielded an alkaline load of -10.9 +/-19.7 mEq/d in the vegetarians compared to an acid load of 13.8 +/- 17.1 mEq/d for the non-vegetarians (p<0.001). The findings of this study indicate that vegetarian food intake produces more alkaline outcomes compared to non-vegetarian diets. The use of the standard PRAL table was sufficient for discrimination between the two diets.


The modern Western-type diet is deficient in fruits and vegetables and contains excessive animal products, generating the accumulation of non-metabolizable anions and a lifespan state of overlooked metabolic acidosis, whose magnitude increases progressively with aging due to the physiological decline in kidney function. In response to this state of diet-derived metabolic acidosis, the kidney implements compensating mechanisms aimed to restore the acid-base balance, such as the removal of the non-metabolizable anions, the conservation of citrate, and the enhancement of kidney ammoniagenesis and urinary excretion of ammonium ions. These adaptive processes lower the urine pH and induce an extensive change in urine composition, including hypocitraturia, hypercalciuria, and nitrogen and phosphate wasting. Low urine pH predisposes to uric acid stone formation. Hypocitraturia and hypercalciuria are risk factors for calcium stone disease. Even a very mild degree of metabolic acidosis induces skeletal muscle resistance to the insulin action and dietary acid load may be an important variable in predicting the metabolic abnormalities and the cardiovascular risk of the general population, the overweight and obese persons, and other patient populations including diabetes and chronic kidney failure. High dietary acid load is more likely to result in diabetes and systemic hypertension and may increase the cardiovascular risk. Results of recent observational studies confirm an association between insulin resistance and metabolic acidosis markers, including low serum bicarbonate, high serum anion gap, hypocitraturia, and low urine pH. Copyright © 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.


The protective effect of vegetables on the risk of breast cancer recurrence is uncertain. We sought to evaluate the association between breast cancer recurrence and vegetable intake including analyses stratified on tamoxifen use. Experimental evidence of anti-carcinogenic activity of phytochemicals in cruciferous vegetables in combination with tamoxifen led to specific evaluation of this class of vegetables as well. To assess the association between vegetable intake and breast cancer recurrence, vegetable intake from repeat 24-h dietary recalls were examined as a secondary analysis of 3,080 breast cancer survivors enrolled in the Women's Healthy Eating and Living (WHEL) Study. At the time of enrollment women were, on average, 23.5 months post-diagnosis. The hazard of recurrence, controlling for relevant and significant clinical and demographic variables, with vegetable intake was assessed overall and separately for women taking tamoxifen. WHEL participants reported mean baseline intakes (⁻x, SE) of 3.1 ± 0.05 and 0.5 ± 0.02 servings/day of total and cruciferous vegetables, respectively. Baseline vegetable intake in the highest as compared to lowest tertiles was associated with an overall lower adjusted hazard ratios (HR) for recurrence of 0.69, 95% CI 0.55-0.87. Among women taking tamoxifen, the HRs were 0.56, 95% CI 0.41-0.77 for total vegetables and 0.65, 95% CI 0.47-0.89 for cruciferous vegetable intake. The hazard in women using tamoxifen who reported cruciferous vegetable intake above the median and who were within the highest tertile of total vegetable intake was HR 0.48; 95% CI 0.32-0.70. This secondary analysis in over 3,000 breast cancer survivors suggests that baseline vegetable intake may be associated with a reduction in the risk of breast cancer recurrent or new events particularly for those using tamoxifen. Such associations should be explored further as the possibility that vegetable intake is simply a surrogate for other health-promoting behaviors cannot be ruled out.


The diagnosis of cancer can motivate survivors to alter their lifestyle habits. Healthcare providers need to be aware of what changes patients are likely to make in order to derive more pertinent recommendations; however, few studies have reported pre- and post-diagnostic lifestyle behaviours. Semi-quantitative food frequency questionnaires (FFQs) completed approximately 1 year after diagnosis were used to evaluate dietary intake and supplement use before and after diagnosis in a cohort of 1,560 breast cancer patients participating in the UK, prospective DietCompLyf study. Intake of fruit and vegetables, wholegrains and lean sources of protein increased significantly post-diagnosis (P < 0.05, each). Conversely, after diagnosis consumption of high-fat, high-sugar products, red meat, coffee, some alcoholic drinks and refined grains significantly decreased (P < 0.05, each). Post-diagnostic changes in diet were accompanied by changes in the intake of macronutrients and a number of vitamins and minerals. Supplement use was highly prevalent (56.1%) pre-diagnosis, increasing to 62.8% after diagnosis (P = 0.001). Fish oils, multivitamin and minerals, and evening primrose oil were most often used and the proportion of users significantly increased (P < 0.05, each) after diagnosis. The percentage of women using oestrogenic botanical supplements (OBSs) was small but more than doubled to 8.4% after diagnosis (P < 0.05). British women participating in the DietCompLyf study reported significant changes in dietary intake and supplement use after their breast cancer diagnosis. These findings contribute to our understanding of female cancer survivors' dietary behaviours which is crucial for developing and implementing recommendations.


Previous studies have suggested that dietary factors may be important in the development of bladder cancer. We examined macronutrient intake in relation to risk of urothelial cell carcinoma among 469,339 men and women in the European Prospective Investigation into Cancer and Nutrition. Associations were examined using Cox regression, stratified by sex, age at recruitment and centre and further adjusted for smoking status and duration, body mass index and total energy intake. After an average of 11.3 years of follow-up, 1,416 new cases of urothelial cell carcinoma were identified. After allowing for measurement error, a 3% increase in the consumption of energy intake from animal protein was associated with a 15% higher risk (95% confidence interval [CI]: 3-30%; p(trend) = 0.01) and a 2% increase in energy from plant protein intake was associated with a 23% lower risk (95% CI: 36-7%, p(trend) = 0.006). Dietary intake of fat, carbohydrate, fibre or calcium was not associated with risk. These findings suggest that animal and/or plant protein may affect the risk of urothelial cell carcinoma, and examination of these associations in other studies is needed. Copyright © 2012 UICC.


OBJECTIVES: Considerable evidence has shown that diet can affect both the incidence and the progression of prostate cancer. The objective of this study was to determine whether men in this situation could make a change to a diet emphasizing plant-based foods and fish and to examine the effect on quality of life (QOL) and prostate-specific antigen (PSA) velocity. METHODS: A total of 36 men and their partners were randomly assigned to attend a series of 11 dietary and cooking classes that also integrated mindfulness practice as a support in making the change or a wait-list control group. Assessments were made of dietary intake, QOL, and PSA at baseline, after intervention (11 weeks), and 3 months after intervention. RESULTS: The intervention group showed significant reductions in the consumption of saturated fat and increased consumption of vegetable proteins with accompanying reductions in animal proteins, including dairy products. They also showed increased QOL. Although no significant change was found in the rate of PSA increase between the two groups, the mean PSA doubling time for the intervention group was substantially longer at the 3-month follow-up visit than that of the controls. CONCLUSIONS: Men with a increasing PSA level after primary treatment were able to make a change to a prostate-healthy diet, accompanied by increases in QOL. No significant difference was found in the log PSA slope between the two groups; however, the PSA doubling time increased substantially in the intervention group compared with that in the controls. Future trials should examine the effect of the prostate-healthy diet with a larger sample of men for a longer period.


Diet may represent a modifiable prostate cancer (CaP) risk factor, but a vegetable-based prostate-healthy diet is a major change for most men. We used a ratio of animal:vegetable proteins (A:V ratio) to evaluate whether a comprehensive dietary change was self-sustaining following completion of 11 weekly dietary and cooking classes that integrated mindfulness training (MT). Thirty-six men with recurring CaP were randomized to the intervention or wait-list control. Assessments were at baseline, three months and six months. Of the 17 men randomized to the intervention, 14 completed the requirements. Nineteen were randomized to control and 17 completed requirements. Compared to controls, a significant post-intervention (3 months) decrease in A:V ratio in the intervention group (p=.01) was self-maintained 3 months post-intervention (p=0.049). At each assessment, the A:V ratio was correlated with lycopene, fiber, saturated fat, and dietary cholesterol; four dietary components linked to clinically relevant outcomes in CaP. Change in A:V ratio was also significantly correlated with changes in fiber, saturated fat and dietary cholesterol intake. Participants reported regular MT practice and there was a significant correlation between MT practice and changes in both initiation and maintenance of the change in the A:V ratio. These pilot results provide encouraging evidence for the feasibility of a dietary program that includes MT in supporting dietary change for men with recurrent CaP and invite further study to explore the possible role of MT as a means of supporting both initiation of dietary changes and maintenance of those changes over time.


Cruciferous vegetables, tomato sauce, and legumes have been associated with reduced risk of incident advanced prostate cancer. In vitro and animal studies suggest these foods may inhibit progression of prostate cancer, but there are limited data in men. Therefore, we prospectively examined whether intake of total vegetables, and specifically cruciferous vegetables, tomato sauce, and legumes, after diagnosis reduce risk of prostate cancer progression among 1,560 men diagnosed with non-metastatic prostate cancer and participating in the Cancer of the Prostate Strategic Urologic Research Endeavor, a United States prostate cancer registry. As a secondary analysis, we also examined other vegetable sub-groups, total fruit, and subgroups of fruits. The participants were diagnosed primarily at community-based clinics and followed from 2004–2009. We assessed vegetable and fruit intake via a semi-quantitative food frequency questionnaire, and ascertained prostate cancer outcomes via urologist report and medical records. We observed 134 events of progression (53 biochemical recurrences, 71 secondary treatments likely due to recurrence, six bone metastases, four prostate cancer deaths) during 3,171 person-yrs. Men in the fourth quartile of post-diagnostic cruciferous vegetable intake had a statistically significant 59% decreased risk of prostate cancer progression compared to men in the lowest quartile (hazard ratio (HR): 0.41; 95% confidence interval (CI): 0.22, 0.76; p-trend: 0.003). No other vegetable or fruit group was statistically significantly associated with risk of prostate cancer progression. In conclusion, cruciferous vegetable intake after diagnosis may reduce risk of prostate cancer progression.


Objective: The chemotherapeutic agent mitoxantrone was approved for use in multiple sclerosis (MS) in 2000. After a review of all the available evidence, the original report of the Therapeutics and Technology Assessment Subcommittee in 2003 concluded that mitoxantrone probably reduced clinical attack rates, MRI activity, and disease progression. Subsequent reports of decreased systolic function, heart failure, and leukemia prompted the US Food and Drug Administration to institute a “black box” warning in 2005. This review was undertaken to examine the available literature on the efficacy and safety of mitoxantrone use in patients with MS since the initial report. Methods: Relevant articles were obtained through a review of the medical literature and the strength of the available evidence was graded according to the American Academy of Neurology evidence classification scheme. Results: The accumulated Class III and IV evidence suggests an increased incidence of systolic dysfunction and therapy-related acute leukemia (TRAL) with mitoxantrone therapy. Systolic dysfunction occurs in ∼12% of patients with MS treated with mitoxantrone, congestive heart failure occurs in ∼0.4%, and leukemia occurs in ∼0.8%. The number needed to harm is 8 for systolic dysfunction and 123 for TRAL. There is no new efficacy evidence that would change the recommendation from the previous report. Conclusions: The risk of systolic dysfunction and leukemia in patients treated with mitoxantrone is higher than suggested at the time of the previous report, although comprehensive postmarketing surveillance data are lacking. GLOSSARY


OBJECTIVE: To examine the relation between retinal artery disease and cerebral small-vessel disease (SVD). METHODS: In a prospective cohort of patients with symptomatic atherosclerotic disease, the authors performed retinal photographs and brain MRI. Two ophthalmologists, not aware of the MR results, independently assessed retinal arterial narrowing, crossings, sclerosis, and tortuosity according to standard scoring lists. Two observers independently assessed white matter lesions (WML) and lacunar infarcts on the MR images. Lesions were considered abnormal only when both ophthalmologists or MR raters agreed. Cerebral SVD was defined as the presence of WML or lacunar infarcts. RESULTS: In 179 patients, retinal photographs and brain MRI were performed. Of the 108 patients with MR signs of SVD, 92% had at least one retinal vascular abnormality; of the 71 patients without SVD, 77% had retinal pathology (p < 0.01). All types of retinal vascular pathology occurred more frequently in patients with SVD, but only retinal arterial narrowing and sclerosis differed significantly. In the 109 normotensive patients, the presence of any retinal vascular change correlated with signs of SVD (p = 0.01). CONCLUSION: Pathologic changes in the retinal arteries parallel changes in the small cerebral arteries that cause WML and lacunes, both in hypertensive and in normotensive patients.


144 multiple sclerosis patients took a low-fat diet for 34 years. For each of three categories of neurological disability (minimum, moderate, severe) patients who adhered to the prescribed diet (less than or equal to 20 g fat/day) showed significantly less deterioration and much lower death rates than did those who consumed more fat than prescribed (greater than 20 g fat/day). The greatest benefit was seen in those with minimum disability at the start of the trial; in this group, when those who died from non-MS diseases were excluded from the analysis, 95% survived and remained physically active.


The purpose of this study was to determine whether a single LDL apheresis would improve impaired endothelium-dependent dilation of the coronary artery in patients with hypercholesterolemia. Hypercholesterolemia is associated with impaired endothelial function, and human studies using cholesterol-lowering drugs indicate that endothelial function in the coronary arteries improves with reduction of serum LDL cholesterol over 6 to 12 months. The internal diameter of the left coronary artery and the coronary blood flow were measured by intracoronary Doppler-wire measurement and quantitative angiography before and immediately after a single LDL apheresis in a population of 15 patients with familial hypercholesterolemia. Endothelium-dependent vasodilation was assessed by intracoronary infusion of acetylcholine (1, 10, and 50 microg/min), and endothelium-independent vasodilation was assessed by intracoronary bolus infusion of isosorbide dinitrate (2.5 mg) or papaverine (10 mg). A single 3-hour LDL apheresis reduced serum LDL cholesterol by an average of 86.6 +/- 1.7%. After the LDL apheresis, the changes in the coronary artery diameter and coronary blood flow in response to an infusion of 50 microg/min of acetylcholine increased significantly compared to the pre-apheresis values (from -19.7 +/- 4.8 to -2.9 +/- 3.0% [P < 0.01] and from 80.7 +/- 27.6 to 155.3 +/- 23.5% [P < 0.01], respectively). The LDL apheresis did not significantly change the response of either parameter to infusion with isosorbide dinitrate or papaverine. The endothelial function of the epicardial coronary artery and the coronary microvasculature improved in hypercholesterolemic patients after only a single LDL apheresis, a procedure that markedly reduces the serum level of LDL cholesterol. Copyright 2004 Wiley-Liss, Inc.


CONTEXT: Interferon beta is widely prescribed to treat multiple sclerosis (MS); however, its relationship with disability progression has yet to be established. OBJECTIVE: To investigate the association between interferon beta exposure and disability progression in patients with relapsing-remitting MS. DESIGN, SETTING, AND PATIENTS: Retrospective cohort study based on prospectively collected data (1985-2008) from British Columbia, Canada. Patients with relapsing-remitting MS treated with interferon beta (n = 868) were compared with untreated contemporary (n = 829) and historical (n = 959) cohorts. MAIN OUTCOME MEASURES: The main outcome measure was time from interferon beta treatment eligibility (baseline) to a confirmed and sustained score of 6 (requiring a cane to walk 100 m; confirmed at >150 days with no measurable improvement) on the Expanded Disability Status Scale (EDSS) (range, 0-10, with higher scores indicating higher disability). A multivariable Cox regression model with interferon beta treatment included as a time-varying covariate was used to assess the hazard of disease progression associated with interferon beta treatment. Analyses also included propensity score adjustment to address confounding by indication. RESULTS: The median active follow-up times (first to last EDSS measurement) were as follows: for the interferon beta-treated cohort, 5.1 years (interquartile range [IQR], 3.0-7.0 years); for the contemporary control cohort, 4.0 years (IQR, 2.1-6.4 years); and for the historical control cohort, 10.8 years (IQR, 6.3-14.7 years). The observed outcome rates for reaching a sustained EDSS score of 6 were 10.8%, 5.3%, and 23.1% in the 3 cohorts, respectively. After adjustment for potential baseline confounders (sex, age, disease duration, and EDSS score), exposure to interferon beta was not associated with a statistically significant difference in the hazard of reaching an EDSS score of 6 when either the contemporary control cohort (hazard ratio, 1.30; 95% CI, 0.92-1.83; P = .14) or the historical control cohort (hazard ratio, 0.77; 95% CI, 0.58-1.02; P = .07) were considered. Further adjustment for comorbidities and socioeconomic status, where possible, did not change interpretations, and propensity score adjustment did not substantially change the results. CONCLUSION: Among patients with relapsing-remitting MS, administration of interferon beta was not associated with a reduction in progression of disability.


It is commonly accepted that nutrition is one of the possible environmental factors involved in the pathogenesis of multiple sclerosis (MS), but its role as complementary MS treatment is unclear and largely disregarded. At present, MS therapy is not associated to a particular diet, probably due to lack of information on the effects of nutrition on the disease. To overcome the distrust of the usefulness of dietary control in MS and to encourage nutritional interventions in the course of the disease, it is necessary to assess the nature and the role of bioactive dietary molecules and their targets, and establish how a dietary control can influence cell metabolism and improve the wellness of MS patients. The aim of this review is to provide a rationale for a nutritional intervention in MS by evaluating at the molecular level the effects of dietary molecules on the inflammatory and autoimmune processes involved in the disease. Present data reveal that healthy dietary molecules have a pleiotropic role and are able to change cell metabolism from anabolism to catabolism and down-regulate inflammation by interacting with enzymes, nuclear receptors and transcriptional factors. The control of gut dysbiosis and the combination of hypo-caloric, low-fat diets with specific vitamins, oligoelements and dietary integrators, including fish oil and polyphenols, may slow-down the progression of the disease and ameliorate the wellness of MS patients. Copyright © 2011 Elsevier Ltd. All rights reserved.


OBJECTIVES: Atherosclerosis begins in childhood and progresses during adolescence and young adulthood. The Pathobiological Determinants of Atherosclerosis in Youth Study previously reported risk scores to estimate the probability of advanced atherosclerotic lesions in young individuals aged 15 to 34 years using the coronary heart disease risk factors (gender, age, serum lipoprotein concentrations, smoking, hypertension, obesity, and hyperglycemia). In this study we investigated the relation of these risk scores to the early atherosclerotic lesions. METHODS: We measured atherosclerotic lesions in the left anterior descending coronary artery, right coronary artery, and abdominal aorta and the coronary heart disease risk factors in persons 15 to 34 years of age who died as a result of external causes and were autopsied in forensic laboratories. RESULTS: Risk scores computed from the modifiable risk factors were associated with prevalence of microscopically demonstrable lesions of atherosclerosis (American Heart Association grade 1) in the left anterior descending coronary artery and with the extent of the earliest detectable gross lesion (fatty streaks) in the right coronary artery and abdominal aorta. Risk scores computed from the modifiable risk factors also were associated with prevalence of lesions of higher degrees of microscopic severity (intermediate as well as advanced) in the left anterior descending coronary artery and with extent of lesions of higher degrees of severity (intermediate and raised lesions) in the right coronary artery and abdominal aorta. CONCLUSIONS: Risk scores calculated from traditional coronary heart disease risk factors to identify individual young persons with high probability of having advanced atherosclerotic lesions also are associated with earlier atherosclerotic lesions, including the earliest anatomically demonstrable atherosclerotic lesion. These results support lifestyle modification in youth to prevent development of the initial lesions and the subsequent progression to advanced lesions and, thereafter, to prevent or delay coronary heart disease.


We assessed the relation of risk factors for cardiovascular disease to early atherosclerotic lesions in the aorta and coronary arteries in 35 persons (mean age at death, 18 years). Aortic involvement with fatty streaks was greater in blacks than in whites (37 vs. 17 percent, P less than 0.01). However, aortic fatty streaks were strongly related to antemortem levels of both total and low-density lipoprotein cholesterol (r = 0.67, P less than 0.0001 for each association), independently of race, sex, and age, and were inversely correlated with the ratio of high-density lipoprotein cholesterol to low-density plus very-low-density lipoprotein cholesterol (r = -0.35, P = 0.06). Coronary-artery fatty streaks were correlated with very-low-density lipoprotein cholesterol (r = 0.41, P = 0.04). Mean systolic blood-pressure levels also tended to be higher in the four subjects with coronary-artery fibrous plaques than in those without them: 112 mm Hg as compared with 104 (P = 0.09). These results document the importance of risk-factor levels to early anatomical changes in the aorta and coronary arteries. The progression of fatty streaks to fibrous plaques is uncertain, but these data suggest that a rational approach to the prevention of cardiovascular disease should begin early in life.


BACKGROUND: Early childhood introduction of nutritional habits aimed at atherosclerosis prevention reduces children's serum total cholesterol concentration, but its effect on vascular endothelial function is unknown. METHODS AND RESULTS: Between 1990 and 1992, we randomized healthy 7-month-old infants (n=1062) to intervention (low-saturated-fat diet) and control (unrestricted diet) groups. At the age of 11 years, endothelium-dependent (flow-mediated) and endothelium-independent (nitrate-mediated) vasodilatory responses of the brachial artery were measured with high-resolution ultrasound in 179 intervention and 190 control children. The effect of intervention on endothelial function was significant in boys (P=0.0034) but not in girls (P=0.69). The maximum endothelium-dependent dilation response (mean+/-SD) was 9.62+/-3.53% and 8.36+/-3.85% in intervention boys and control boys and 8.84+/-4.00% and 8.44+/-3.60% in intervention girls and control girls, respectively. Intervention had no effect on nitrate-mediated dilation. The difference in endothelial function in boys remained significant after adjustment for current serum total or LDL cholesterol but became nonsignificant after adjustment for mean cholesterol measured under 3 years of age (adjusted means: 9.46% [CI 8.68% to 10.24%] versus 8.54% [CI 7.75% to 9.32%], P=0.11). CONCLUSIONS: A low-saturated-fat diet introduced in infancy and maintained during the first decade of life is associated with enhanced endothelial function in boys. The effect is explained in part by the diet-induced reduction in serum cholesterol concentration.


Most metastatic tumors, such as those originating in the prostate, lung, and gastrointestinal tract, respond poorly to conventional chemotherapy. Novel treatment strategies for advanced cancer are therefore desperately needed. Dietary restriction of the essential amino acid methionine offers promise as such a strategy, either alone or in combination with chemotherapy or other treatments. Numerous in vitro and animal studies demonstrate the effectiveness of dietary methionine restriction in inhibiting growth and eventually causing death of cancer cells. In contrast, normal host tissues are relatively resistant to methionine restriction. These preclinical observations led to a phase I clinical trial of dietary methionine restriction for adults with advanced cancer. Preliminary findings from this trial indicate that dietary methionine restriction is safe and feasible for the treatment of patients with advanced cancer. In addition, the trial has yielded some preliminary evidence of antitumor activity. One patient with hormone-independent prostate cancer experienced a 25% reduction in serum prostate-specific antigen (PSA) after 12 weeks on the diet, and a second patient with renal cell cancer experienced an objective radiographic response. The possibility that methionine restriction may act synergistically with other cancer treatments such as chemotherapy is being explored. Findings to date support further investigation of dietary methionine restriction as a novel treatment strategy for advanced cancer.


Recent studies confirm that dietary methionine restriction increases both mean and maximal lifespan in rats and mice, achieving "aging retardant" effects very similar to those of caloric restriction, including a suppression of mitochondrial superoxide generation. Although voluntary caloric restriction is never likely to gain much popularity as a pro-longevity strategy for humans, it may be more feasible to achieve moderate methionine restriction, in light of the fact that vegan diets tend to be relatively low in this amino acid. Plant proteins - especially those derived from legumes or nuts - tend to be lower in methionine than animal proteins. Furthermore, the total protein content of vegan diets, as a function of calorie content, tends to be lower than that of omnivore diets, and plant protein has somewhat lower bioavailability than animal protein. Whole-food vegan diets that moderate bean and soy intake, while including ample amounts of fruit and wine or beer, can be quite low in methionine, while supplying abundant nutrition for health (assuming concurrent B12 supplementation). Furthermore, low-fat vegan diets, coupled with exercise training, can be expected to promote longevity by decreasing systemic levels of insulin and free IGF-I; the latter effect would be amplified by methionine restriction - though it is not clear whether IGF-I down-regulation is the sole basis for the impact of low-methionine diets on longevity in rodents.


Methionine is an essential amino acid with many key roles in mammalian metabolism such as protein synthesis, methylation of DNA and polyamine synthesis. Restriction of methionine may be an important strategy in cancer growth control particularly in cancers that exhibit dependence on methionine for survival and proliferation. Methionine dependence in cancer may be due to one or a combination of deletions, polymorphisms or alterations in expression of genes in the methionine de novo and salvage pathways. Cancer cells with these defects are unable to regenerate methionine via these pathways. Defects in the metabolism of folate may also contribute to the methionine dependence phenotype in cancer. Selective killing of methionine dependent cancer cells in co-culture with normal cells has been demonstrated using culture media deficient in methionine. Several animal studies utilizing a methionine restricted diet have reported inhibition of cancer growth and extension of a healthy life-span. In humans, vegan diets, which can be low in methionine, may prove to be a useful nutritional strategy in cancer growth control. The development of methioninase which depletes circulating levels of methionine may be another useful strategy in limiting cancer growth. The application of nutritional methionine restriction and methioninase in combination with chemotherapeutic regimens is the current focus of clinical studies. Copyright © 2012 Elsevier Ltd. All rights reserved.


Methionine dependence is a metabolic defect that occurs in many human tumor cell lines but not normal in unestablished cell strains. Methionine-dependent tumor cell lines are unable to proliferate and arrest in the late S/G2 phase of the cell cycle when methionine is replaced by its immediate precursor homocysteine in the culture medium (MET-HCY+ medium). However, it is not known whether methionine dependence occurs in fresh patient tumors as it does in cell lines. In order to determine whether methionine dependence occurs in fresh patient tumors as well as whether methionine dependence occurs in fresh patient tumors as well as in cell lines we took advantage of the technique of sponge-gel-supported histoculture to grow tumors directly from surgery. We then measured nuclear DNA content by image analysis to determine the cell cycle position in MET-HCY+ compared to MET+HCY- medium in 21 human patient tumors. Human tumor cell lines found to be methionine dependent by cell count were used as positive controls and were found to have marked reduction of cells in G1 compared to total cells in the cell cycle in MET-HCY+ medium with respect to the G1: total cell ratio in MET+HCY- medium. Therefore late cell cycle arrest was used as a marker of methionine dependence for histocultured patient tumors. We found that 5 human tumors of 21, including tumors of the colon, breast, ovary, prostate, and a melanoma, were methionine dependent based on cell cycle analysis. These data on fresh human tumors indicate that methionine dependence may frequently occur in the cancer patient population. Implications for potential therapy based on methionine dependence are discussed.


Various pesticides are being used to destabilize, perturb, or inhibit crucial biochemical and physiological targets related to metabolism, growth, development, nervous communication, or behavior in pestiferous organisms. Chitin is an eukaryotic extracellular aminosugar biopolymer, massively produced by most fungal systems and by invertebrates, notably arthropods. Being an integral supportive component in fungal cell wall, insect cuticle, and nematode egg shell, chitin has been considered as a selective target for pesticide action. Throughout the elaborate processes of chitin formation and deposition, only the polymerization events associated with the cell membrane compartment are so far available for chemical interference. Currently, the actinomycetes-derived nucleoside peptide fungicides such as the polyoxins and the insecticidal benzoylaryl ureas have reached commercial pesticide status. The polyoxins and other structurally-related antibiotics like nikkomycins are strong competitive inhibitors of the polymerizing enzyme chitin synthase. The exact biochemical lesion inflicted by the benzoylaryl ureas is still elusive, but a post-polymerization event, such as translocation of chitin chains across the cell membrane, is suggested. Hydrolytic degradation of the chitin polymer is essential for hyphal growth, branching, and septum formation in fungal systems as well as for the normal molting of arthropods. Recently, insect chitinase activity was strongly and specifically suppressed by allosamidin, an actimomycetes-derived metabolite. In part, the defense mechanism in plants against invasion of pathogens is associated with induced chitinases. Chitin, chitosan, and their oligomers are able to act as elicitors which induce enhanced levels of chitinases in various plants. Lectins which bind to N-acetyl-D-glucosamine strongly interfere with fungal and insect chitin synthases. Plant lectins with similar properties may be involved in plant-pathogen interaction inter alia by suppressing fungal invasion.


Conventional chemotherapies have showed their limits, notably for patients with advanced cancer. New therapeutic strategies must be identified, and the metabolic abnormalities of cancer cells offer such opportunities. Many human cancer cell lines and primary tumors have absolute requirements for methionine, an essential amino acid. In contrast, normal cells are relatively resistant to exogenous methionine restriction. The biochemical mechanism for methionine dependency has been studied extensively, but the fundamental mechanism remains unclear. A number of investigators have attempted to exploit the methionine dependence of tumors for therapeutic effects in vivo. To reduce in vivo methionine in plasma and tumours, dietary and pharmacological treatments have been used. Methionine-free diet or methionine-deprived total parenteral nutrition causes regression of a variety of animal tumours. Alternatively, methionine depletion was achieved by the use of methioninase. This enzyme specifically degrades methionine and inhibits tumour growth in preclinical models. Because of potential toxicity and quality of life problems, prolonged methionine restriction with diet or with methioninase is not suitable for clinical use. Methionine restriction may find greater application in association with various chemotherapeutic agents. Several preclinical studies have demonstrated synergy between methionine restriction and various cytotoxic chemotherapy drugs. The experimental results accumulated during the last three decades suggest that methionine restriction can become an additional cancer therapeutic strategy, notably in association with chemotherapy.


INTRODUCTION: Amino acid auxotrophy or the metabolic defect which renders cancer incapable of surviving under amino acid depleted conditions is being exploited and explored as a therapeutic against cancer. Early clinical data on asparagine- and arginine-depleting drugs have demonstrated low toxicity and efficacy in melanoma, hepatocellular carcinoma and acute lymphoblastic leukemia. Methionine auxotrophy is a novel niche currently under exploration for targeting certain cancers. AREAS COVERED: In this review we explore the discovery of methionine auxotrophy followed by in vitro, in vivo and patient data on targeting cancer with methionine depletion. We end with a small discussion on bioengineering, pegylation and red blood cell encapsulation as mechanisms for decreasing immunogenicity of methionine-depleting drugs. We hope to provide a platform for future pharmacology, toxicology and cytotoxicity studies with methionine depletion therapy and drugs. EXPERT OPINION: Although methionine auxotrophy seems as a viable target, extensive research addressing normal versus cancer cell toxicity needs to be conducted. Further research also needs to be conducted into the molecular mechanism associated with methionine depletion therapy. Finally, novel methods need to be developed to decrease the immunogenicity of methionine-depleting drugs, a current issue with protein therapeutics.


BACKGROUND AND AIMS: The mechanisms of cancer cell growth and metastasis are still not entirely understood, especially from the viewpoint of chemical reactions in tumours. Glycolytic metabolism is markedly accelerated in cancer cells, causing the accumulation of glucose (a reducing sugar) and methionine (an amino acid), which can non-enzymatically react and form carcinogenic substances. There is speculation that this reaction produces gaseous sulfur-containing compounds in tumour tissue. The aims of this study were to clarify the products in tumour and to investigate their effect on tumour proliferation. METHODS: Products formed in the reaction between glucose and methionine or its metabolites were analysed in vitro using gas chromatography. Flatus samples from patients with colon cancer and exhaled air samples from patients with lung cancer were analysed using near-edge x-ray fine adsorption structure spectroscopy and compared with those from healthy individuals. The tumour proliferation rates of mice into which HT29 human colon cancer cells had been implanted were compared with those of mice in which the cancer cells were surrounded by sodium hyaluronate gel to prevent diffusion of gaseous material into the healthy cells. RESULTS: Gaseous sulfur-containing compounds such as methanethiol and hydrogen sulfide were produced when glucose was allowed to react with methionine or its metabolites homocysteine or cysteine. Near-edge x-ray fine adsorption structure spectroscopy showed that the concentrations of sulfur-containing compounds in the samples of flatus from patients with colon cancer and in the samples of exhaled air from patients with lung cancer were significantly higher than in those from healthy individuals. Animal experiments showed that preventing the diffusion of sulfur-containing compounds had a pronounced antitumour effect. CONCLUSIONS: Gaseous sulfur-containing compounds are the main products in tumours and preventing the diffusion of these compounds reduces the tumour proliferation rate, which suggests the possibility of a new approach to cancer treatment.


Available information indicates that long-lived mammals have low rates of reactive oxygen species (ROS) generation and oxidative damage at their mitochondria. On the other hand, many studies have consistently shown that dietary restriction (DR) in rodents also decreases mitochondrial ROS (mtROS) production and oxidative damage to mitochondrial DNA and proteins. It has been observed that protein restriction also decreases mtROS generation and oxidative stress in rat liver, whereas neither carbohydrate nor lipid restriction change these parameters. This is interesting because protein restriction also increases maximum longevity in rodents (although to a lower extent than DR) and is a much more practicable intervention for humans than DR, whereas neither carbohydrate nor lipid restriction seem to change rodent longevity. Moreover, it has been found that isocaloric methionine restriction also decreases mtROS generation and oxidative stress in rodent tissues, and this manipulation also increases maximum longevity in rats and mice. In addition, excessive dietary methionine also increases mtROS generation in rat liver. These studies suggest that the reduced intake of dietary methionine can be responsible for the decrease in mitochondrial ROS generation and the ensuing oxidative damage that occurs during DR, as well as for part of the increase in maximum longevity induced by this dietary manipulation. In addition, the mean intake of proteins (and thus methionine) of Western human populations is much higher than needed. Therefore, decreasing such levels to the recommended ones has a great potential to lower tissue oxidative stress and to increase healthy life span in humans while avoiding the possible undesirable effects of DR diets.


In the fall of 2007, the Minnesota Department of Health was notified of 11 cases of an unexplained neurological illness, all linked to a pork processing plant, Quality Pork Processors, Inc., in Austin, MN. The cluster of workers had been experiencing similar symptoms, including fatigue, pain, numbness, and tingling in their extremities as well as weakness. The symptoms were described as more sensory than motor, and all patients had evidence of polyradiculoneuropathy with signs of nerve root irritation. An epidemiological investigation revealed that the only commonality between cases was their exposure to a pork brain extraction procedure involving compressed air. As relatives of the cases remained asymptomatic and all cultures for known pathogens were negative, the etiology of the syndrome seemed not to be infectious. Clinically, the syndrome was most akin to chronic inflammatory demyelinating polyneuropathy. Laboratory tests corroborated the clinical findings, revealing inflammation of peripheral nerves and nerve roots; however, these cases also had features clinically distinct from chronic inflammatory demyelinating polyneuropathy as well as laboratory testing revealing a novel immunoglobulin G immunostaining pattern. This suggested that the observed inflammation was the result of 1 or more unidentified antigens. This syndrome was ultimately dubbed progressive inflammatory neuropathy and was theorized to be an autoimmune reaction to aerosolized porcine neural tissue. Since the investigation's outset, 18 cases of progressive inflammatory neuropathy have been identified at the Minnesota pork processing plant, with 5 similar cases at an Indiana plant and 1 case at a Nebraskan plant. The plants in which cases have been identified have since stopped the use of compressed air in removing pork brains. All cases have stabilized or improved, with some requiring immunosuppressive and analgesic treatment. The study of progressive inflammatory neuropathy is ongoing, and the details of this investigation highlight the value of epidemiological principles in the identification and containment of outbreaks while researchers attempt to uncover the unique pathophysiology and potential etiology of the illness. Mt Sinai J Med 76:442-447, 2009. (c) 2009 Mount Sinai School of Medicine.


The human APOBEC3G protein is an innate anti-viral factor that can dominantly inhibit the replication of some endogenous and exogenous retroviruses. The prospects of purposefully harnessing such an anti-viral defense are under investigation. Here, long-term co-culture experiments were used to show that porcine endogenous retrovirus (PERV) transmission from pig to human cells is reduced to nearly undetectable levels by expressing human APOBEC3G in virus-producing pig kidney cells. Inhibition occurred by a deamination-independent mechanism, likely after particle production but before the virus could immortalize by integration into human genomic DNA. PERV inhibition did not require the DNA cytosine deaminase activity of APOBEC3G and, correspondingly, APOBEC3G-attributable hypermutations were not detected. In contrast, over-expression of the sole endogenous APOBEC3 protein of pigs failed to interfere significantly with PERV transmission. Together, these data constitute the first proof-of-principle demonstration that APOBEC3 proteins can be used to fortify the innate anti-viral defenses of cells to prevent the zoonotic transmission of an endogenous retrovirus. These studies suggest that human APOBEC3G-transgenic pigs will provide safer, PERV-less xenotransplantation resources and that analogous cross-species APOBEC3-dependent restriction strategies may be useful for thwarting other endogenous as well as exogenous retrovirus infections.


Background Few studies have investigated mortality in seafood workers worldwide, and no such study has been conducted in the United States. The objective of this study was to investigate mortality in American seafood workers. Methods The study population was derived from 4 states and consisted of 4116 subjects who worked mainly in seafood processing plants. They were followed up from 1966 to 2003. Standardized mortality ratios (SMRs) and proportional mortality ratios (PMRs) were estimated, using the US general population for comparison. Results About 45% of the cohort was born after 1949. A total of 788 deaths were recorded; 53% of the decedents were female, and 88% were white. The SMRs for stomach cancer and disorders of the thyroid gland in the cohort as a whole were 2.1 (95% confidence interval [CI], 1.1–3.8) and 6.1 (95% CI 1.3–18.0), respectively. The SMRs for breast cancer, and occlusion/stenosis of the pre-cerebral/cerebral arteries in the cohort as a whole were 0.5 (95% CI, 0.3–0.9) and 0.5 (95% CI, 0.2–0.8), respectively. The SMR for ischemic heart disease in white females was 0.8 (95% CI, 0.6–0.9). Conclusions This cohort had excess deaths from stomach cancer and disorders of the thyroid gland, and deficit of deaths from breast cancer, stroke and ischemic heart disease. The significance of these findings is unknown, especially as less than 20% of the cohort were deceased. Nevertheless, the cohort is unique and important, and further follow-up may shed more light on mortality patterns in this occupational group.


In November 2007 a novel neuropathy, immune-mediated polyradiculoneuropathy (IP), was identified among workers at a Minnesota swine abattoir where a unique compressed air technique was used to remove porcine brains. An epidemiologic investigation at another abattoir in Indiana that also uses this process was launched to evaluate workers self-reporting neurologic illness compatible with IP. A nested case-control study was performed to identify cases and risk factors. Six confirmed, one probable, and three possible IP cases were detected. IP cases were 28-52 years old, of Latino origin, and 62.5% female. Onset dates ranged from April 2005-December 2007; 60% were hospitalized. IP cases at this plant were similar in clinical presentation and exposure risks to those detected in Minnesota. Swine abattoirs using similar brain extraction methods should discontinue this process.


BACKGROUND AND AIM: The occurrence of malignant pleural mesothelioma (MPM) has been reported among population groups with no documented professional exposure to asbestos fibres living in different geographic areas. This paper reviews existing data related to non occupational MPM including its occurrence in the province of Catania (Sicily, Italy). METHODS: An electronic search of literature related to non occupational MPM was performed including the year 2005. RESULTS: Non occupational MPM in subjects living in areas contaminated by a variety of asbestos and non asbestos fibres has been well documented through a number of epidemiologic studies including cases series, case-control studies, and a cohort study. In addition, the observation of familial clustering of MPM, suggests that genetic factors may play a role in the pathogenesis of this malignancy. The epidemiological evidence also suggests that MPM may occur as a result of the interaction between environmental carcinogens, genetic factors, and virus infection. CONCLUSION: It is likely that genetic predisposition and non-occupational exposure to low doses of asbestos and asbestos-like fibres may concur to the development of malignant mesothelioma. However, additional epidemiological and laboratory studies are needed to further understand the relationship between environmental exposure and individual susceptibility to this malignancy.


OBJECTIVES: Occupation as a farmer has been associated with increased risks of haematological cancers in adults. This study aimed to examine whether farm exposures in childhood contribute to these risks, by using parental occupation in farming as a proxy for growing up on a farm. METHODS: New Zealand death records (1998-2003) of persons aged 35-85 were extracted (n=114 289). For 82.3% usual occupation and the occupation of at least one of the parents could be coded (n=94 054). Unconditional logistic regression analyses included 3119 haematological cancer deaths (cases) and 90 935 deaths from other causes (controls). ORs for farming and growing up on a farm were adjusted for each other, year of birth, age at death, socio-economic status, Māori ethnicity, immigration status and sex. RESULTS: Growing up on a livestock farm was positively associated with haematological cancer (OR 1.22, 95% CI 1.05 to 1.41), particularly for poultry farms (OR 2.99, 95% CI 1.44 to 6.21), while growing up on a crop farm was not (OR 0.81, 95% CI 0.64 to 1.03). Crop farming in adulthood was associated with an increased haematological cancer risk (OR 1.49, 95% CI 1.13 to 1.96), while livestock farming was not (OR 0.80, 95% CI 0.63 to 1.00), except for beef cattle farming (OR 2.99, 95% CI 1.28 to 7.00). These results did not change appreciably when different control groups with different causes of death were used. CONCLUSIONS: These results could suggest a role for early life biological exposures in the development of haematological cancers.


OBJECTIVE: workers in slaughterhouses and processing plants that handle pigs, and pork butchers/meatcutters have been little studied for health risks associated with employment, in spite of the fact that they are potentially exposed to oncogenic and non-oncogenic transmissible agents and chemical carcinogens at work. We report here on an update of mortality in 510 workers employed in abattoirs and processing plants that almost exclusively handled pigs and pork products. METHODS: standardized mortality ratios (SMRs) were estimated for the cohort as a whole, and in subgroups defined by race and sex, using the corresponding US general population mortality rates for comparison. Study subjects were followed up from January 1950 to December 2006, during which time 45% of them died. RESULTS: mortality was significantly increased overall in the cohort. A statistically significant excess of deaths was observed for colon and lung cancers in the entire cohort, SMR=2.7 (95% CI, 1.2-5.1), SMR=1.8 (95% CI, 1.1-2.7), respectively. Significant SMRs in the cohort as a whole were also observed for senile and pre-senile psychotic conditions (SMR=5.1, 95% CI, 1.4-13.1), and pneumonia (SMR=2.6, 95% CI, 1.3-4.8). An observed excess of subarachnoid hemorrhage was seen mainly in whites (SMR=10.1, 95% CI, 1.2-36.3). There was a suggestion of an excess of deaths from ischemic heart disease also, but the elevated SMR was confined to men and was not statistically significant. CONCLUSION: this study confirms the excess occurrence of lung and colon cancers, and stroke previously reported in this occupational group. New findings are the excess of risk for senile and pre-senile psychotic conditions and pneumonia, which together with the excess of colon cancer appear specific for pig/pork workers, as they were not evident in much larger studies of workers in abattoirs and processing plants handling cattle and sheep. However, caution should be exercised in interpreting these findings, since some of them could have occurred by chance, resulting from our examination of a large number of causes of death in multiple study subgroups. For the moment, the significance of these findings remains unknown until they are confirmed in larger studies of adequate statistical power. Studies that will take into account possible occupational and non-occupational confounding factors are needed. Copyright © 2011. Published by Elsevier Inc.