Pseudo-anticipation in Creutzfeldt-Jakob disease is due to a rhomboid-shaped artifact.

BACKGROUND AND PURPOSE: Previous studies have reported conflicting results regarding possible anticipation in familial E200K Creutzfeldt-Jakob disease (fCJD). Our objective was to use a large database to assess the age of disease onset (AODO) in CJD. METHODS: The study population included 477 CJD patients [266 with fCJD, 145 with sporadic CJD (sCJD) and 66 patients of Libyan origin but negative family history] from the Israeli registry of CJD conducted since 1954. In all patients, AODO in relatives and family trees was documented. Comparison of AODO was done using a paired t test and regression using Pearson correlation for birth and year of onset. RESULTS: The initial analysis in 52/73 families in which more than one generation was affected revealed an AODO of 63.30 ± 9.44 in the first generation compared to 56.96 ± 8.99 in the second generation (P < 0.001). However, inspection of individual AODO values plotted by year of birth showed a clear rhomboid methodological artifact generated by missing data of many young onset CJD patients who died before the database began to function in 1954 and of many late onset CJD patients missing at the present time since they will only develop the disease in the future. The 'generation' effect completely disappears if analysis is performed by year of disease onset or for the periods in which complete data are available. CONCLUSIONS: In this very large dataset, true anticipation in fCJD patients was not detected. It is plausible that previous reports supporting the presence of anticipation are biased by a rhomboid-shaped data availability artifact.

Unusual presentations in patients with E200K familial Creutzfeldt-Jakob disease.

BACKGROUND AND PROPOSE: Familial Creutzfeldt-Jakob disease (fCJD) in Jews of Libyan ancestry is caused by an E200K mutation in the PRNP gene. The typical presenting symptoms include cognitive decline, behavioral changes and gait disturbances; however, some patients may have an unusual presentation such as a stroke-like presentation, alien hand syndrome or visual disturbances. The aim of this paper is to describe uncommon presentations in our series of consecutive patients with E200K fCJD. METHODS: The study group included consecutive fCJD patients followed up as part of a longitudinal prospective study ongoing since 2003 or hospitalized since 2005. The clinical diagnosis of probable CJD was based on accepted diagnostic criteria and supported by typical magnetic resonance imaging, electroencephalographic findings, elevated cerebrospinal fluid tau protein levels and by genetic testing for the E200K mutation. Disease symptoms and signs were retrieved from the medical files. RESULTS: The study population included 77 patients (42 men) with a mean age of disease onset of 60.6 ± 7.2 years. The most prevalent presenting symptoms were cognitive decline followed by gait impairment and behavioral changes. However, six patients had an unusual presentation including auditory agnosia, monoparesis, stroke-like presentation, facial nerve palsy, pseudobulbar syndrome and alien hand syndrome. CONCLUSIONS: Our case series illustrates the wide phenotypic variability of the clinical presentation of patients with fCJD and widens the clinical spectrum of the disease. A high level of clinical suspicion may prove useful in obtaining early diagnosis and therefore avoiding costly and inefficient diagnostic and therapeutic strategies.

CSF tau correlates with CJD disease severity and cognitive decline.

BACKGROUND: Creutzfeldt-Jakob disease (CJD) is the most common prion disease in humans. The clinical diagnosis of CJD is supported by a combination of electroencephalogram, MRI, and the presence in the CSF of biomarkers. CSF tau is a marker for neuronal damage and tangle pathology, and is correlated with cognitive status in Alzheimer's disease (AD). OBJECTIVES: The aim of this study was to test whether tau levels in the CSF also correlate with the degree of the neurological deficit and cognitive decline in patients with CJD as reflected by various clinical scales that assess disease severity and cognitive performance. METHODS: Consecutive patients with familial CJD (fCJD) were examined by a neurologist who performed several tests including minimental status examination (MMSE), frontal assessment battery (FAB), NIH stroke scale (NIHSS), CJD neurological scale (CJD-NS), and the expanded disability status scale (EDSS). CSF tau was tested as part of the workout, and the correlation was tested using Pearson correlation. RESULTS: Fifty-two patients with fCJD were recruited to the study (35 males, mean age 59.4 ± 5.7, range 48-75 years). A significant negative correlation was found between CSF tau levels and the cognitive performance of the patients as reflected by their MMSE and FAB scores. In addition, a significant positive correlation was found between tau levels and the clinical disease severity scales of CJD-NS, NIHSS, and EDSS. CONCLUSION: The correlation between tau levels and the disease severity and degree of cognitive decline in patients with fCJD suggests that tau can be a biomarker reflecting the extent of neuronal damage.

Seizures in E200K familial and sporadic Creutzfeldt-Jakob disease.

BACKGROUND: Although seizures (other than myoclonus) are frequently reported in Creutzfeldt-Jakob disease (CJD), their frequency, clinical manifestations, and effect on the disease course is unknown. OBJECTIVES: To characterize the frequency of seizures in E200K familial and sporadic CJD, to describe its semiology, EEG and MRI findings. METHODS: In this retrospective study, we reviewed all patients with CJD who were seen in the Sheba Medical Center between the years 2003-2012 and underwent clinical evaluation, genetic testing, EEG and MRI studies. The diagnosis of seizures was carried out based on documentation of episodes consistent with seizures or episode of unresponsiveness correlated with ictal activity in EEG. RESULTS: Sixty-four probable patients with CJD were included in the study, 57 (89%) with E200K familial (fCJD) and 7 (11%) with sporadic (sCJD). Seizures occurred in 8 patients: 3 of 7 (43%) in patients with sCJD compared to 5/57 (9%) in patients with E200K fCJD (P = 0.04, chi-square test). Two of E200K fCJD patients with seizures had other non-prion etiologies for seizures (brain metastasis, known history of temporal lobe epilepsy which started 44 years before the diagnosis of CJD). Seizures occurred late in the course of the disease with an average of 12 days between the onset of seizures and death. CONCLUSION: Seizures in E200K fCJD were infrequent and occurred late in the disease course. This difference suggests that E200K fCJD represents a separate subtype of the disease with distinct clinical characteristics.

The Creutzfeldt-Jakob disease (CJD) neurological status scale: a new tool for evaluation of disease severity and progression.

OBJECTIVES: To develop a scale sensitive for the neurological manifestations of Creutzfeldt-Jakob disease (CJD). METHODS: A 26-item CJD neurological status scale (CJD-NS) was created based on characteristic disease manifestations. Each sign was assigned to one of eight neurological systems to calculate a total scale score (TSS) and a system involvement score (SIS). The scale was administered to 37 CJD patients, 101 healthy first-degree relatives of the patients and 14 elderly patients with Parkinson's disease (PD). RESULTS: The mean TSS (±SD) was significantly higher in patients with CJD (13.19 ± 5.63) compared with normal controls (0.41 ± 0.78) and PD patients (9.71 ± 3.05). The mean SIS was also significantly different between the CJD (5.19 ± 1.22) and PD (2.78 ± 1.18 P ≤ 0.01) groups reflecting the disseminated nature of neurological involvement in CJD. Using a cutoff of TSS > 4 yielded a sensitivity of 97% for CJD, and specificity of 100% against healthy controls. All individual items showed excellent specificity against healthy subjects, but sensitivity was highly variable. Repeat assessments of CJD patients over 3-9 months revealed a time-dependent increase in both the TSS and the SIS reflecting the scale's ability to track disease progression. CONCLUSIONS: The CJD-NS scale is sensitive to neurological signs and their progression in CJD patients.

Levels of urea in the blood and urine of rats fed raw and heated soybean meal.

Protein from many sources show negative correlation between their biological values and the levels of urea in the blood or urine of rats or pigs. On the basis of the difference in protein quality between raw and heated soybeans, it would be predicted that there should be a higher level of urea in the blood and urine of rats fed raw soybean meal. In the present study, however, little or no difference in the levels of urea in the blood and urine of animals fed raw or autoclaved soybean meal could be demonstrated. It is postulated that the increased catabolism of the poor quality protein of raw soybeans may be masked by a concomitant depression of liver arginase activity and/or a decrease in the total quantity of amino acids available for catabolism because of lower digestibility of the raw soybean protein.

Enhanced urinary trypsin inhibitory activity in gentamicin-induced nephrotoxicity in rats.

We delineated in rats, the relationship between trypsin inhibitory activity in the urine and the nephrotoxic effects of gentamicin, eg, proteinuria and deterioration of glomerular filtration rate (GFR), measured by creatinine clearance. Gentamicin, 70 mg/kg per day, was injected intraperitoneally for 6-10 successive days. Serum and urine gentamicin levels were determined by a microbiological test. Trypsin inhibitory activity was assayed by the casein digestion method. The results showed a steady increase in urinary trypsin inhibitory activity starting from the fourth injection day. The increased levels of urinary trypsin inhibitory activity were associated with increased levels of urinary gentamicin excretion (r = 0.36, p less than 0.02, n = 50 after the fourth injection day), and were significantly higher than in control groups (p less than 0.001). The urinary trypsin inhibitory activity was inversely correlated with the GFR (r = -0.45, p less than 0.01, after the second injection day). The serum trypsin inhibitory activity remained unchanged throughout the study period in all groups. These data suggest that increased urinary trypsin inhibitory activity may be involved in the pathogenesis of gentamicin-induced nephrotoxicity.

Enrichment of poultry products with omega3 fatty acids by dietary supplementation with the alga Nannochloropsis and mantur oil.

Experiments were conducted to evaluate the efficiency of the microalga Nannochloropsis sp. (Nanno.), as a supplement to laying hens' diet, for the production of enriched eggs and meat with omega3 fatty acids (FA). Nanno. has a unique FA composition, namely, the occurrence of a high concentration of eicosapentaenoic acid (EPA; 20:5 omega3) and the absence of other omega3 FA. The effect of supplementing diets with Nanno. on omega3 FA levels in eggs, plasma, liver, and thigh muscle was compared to that of mantur oil, high in alpha-linolenic acid (LNA; 18:3 omega3). Nanno. is rich also in carotenoids, which may be useful for egg yolk pigmentation. The observed effect of Nanno. supplementation on yolk pigmentation was dose responsive, in both the rate of coloration and the color intensity. Addition of enzyme preparations (glucanase plus cellulase or glucanase plus pectinase) slightly elevated the yolk color score. The most prominent changes in the level of omega3 FA in egg yolk were evident when the diets were supplemented with 1% Nanno. or mantur lipid extracts. Levels of dietary algal meal (0.1-1.0%) had low and inconsistent effects on the level of yolk omega3 FA. Algal EPA is not accumulated in the liver or in the egg yolk; it is apparently converted and deposited as docosahexaenoic acid (DHA). LNA from mantur oil was partially converted to DHA, and both DHA and LNA were deposited in egg yolks and livers. It is suggested that the absence of DHA and EPA from thigh muscle is due to the small amount of dietary omega3 FA used in this work, compared to other studies, and to the possibility that in laying hens the egg yolk has a priority on dietary FA over that of muscles.

Accentuated response to soybean inhibitors by meal-feeding in various species.

Diets containing raw soybean products (RSD) fed ad libitum caused a reduction in food consumption and growth, pancreatic enlargement, hypersecretion of digestive enzymes, and enlargement of intestinal segments and their contents in rats, chicks and geese. These effects were found to be related to the concentration of trypsin inhibitor (TI) in the diet. Geese were more sensitive than rats and chicks. Calves fed RSD did not respond in pancreatic hypertrophy and hypersecretion of digestive enzymes, but growth was depressed. Meal-feeding also caused enlargement of the pancreas, digestive tract segments and their contents. The effects of feeding RSD and of meal feeding were found to be additive. In ad libitum feeding the animal can regulate food consumption and moderate the effects of antinutritional factors in the diet. Meal or tube-feeding interfered with this defense mechanism and the negative effects of RSD were accentuated and were lethal in non adapted rats and geese. In long-term studies the incidence of pancreatic nodules was correlated to the level of TI in the diet. Feeding RSD potentiated the carcinogenic effect of azaserine and meal feeding enhanced the incidence and size of the pancreatic nodules in rats fed RSD.

Dietary effects on fat deposition and fatty acid profiles in muscle and fat depots of Friesian bull calves.

Dietary effects on fat deposition, cholesterol level, and fatty acid profiles of muscle and fat depots in Friesian bull calves were evaluated in two trials. In Trial 1 (eight pens of seven Friesian bull calves), three levels of ME (10.4, 10.9, 11.7 MJ/kg of DM; diets L, M and H, respectively) were offered to three groups of calves throughout the entire experimental period. Calves of the fourth group were fed diet M for the first 80 d and diet L thereafter (Treatment ML). Calves were 185 +/- 15 d of age and 215 +/- 18 kg BW at the start of the trial and were slaughtered when they reached a predetermined equal degree of fatness, in a BW range of 480 to 580 kg, and an age range of 417 to 548 d. In Trial 2, four groups of calves (eight pens of seven Friesian bull calves) had free access to diets of the same ME (11.7 MJ/kg of DM) but that differed in either CP content (11.3 vs 13.4%) or had poultry litter substituted for part of soybean meal at the equivalent CP. Calves were 18o +/- 13 d of age and 240 +/- 19 kg BW at the start of the trial and were slaughtered after 232 +/- 11 d, at 508 +/- 22 kg BW. In both trials, dressing percentages and carcass percentages of kidney, pelvic, and cod fat depots were recorded at slaughter, and samples of the 12th rib longissimus muscle with its subcutaneous fat were obtained for lipid analyses. Increasing the ME concentration shortened the growing period and tended to increase carcass depot fat percentage.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of a fat-mobilizing substance from geese urine on geese and chickens.

A fat-mobilizing substance (FMS) was extracted from the urine of fasting, ad-libitum-fed or over-fed colostomized geese. Injection of these materials into geese and cockerels caused increases in plasma-free fatty acids (FFA). A marked anorexigenic effect was obtained in cockerels only, by the FMS obtained from ad-libitum-fed geese. The daily amount of FMS excreted in the urine was proportional to the amount of feed consumed.

Evaluation of simultaneous selection for live body weight and against abdominal fat in broilers.

Three hundred chickens from pedigree matings in a commercial female grandparent stock were slaughtered at 7 or 9 weeks of age. Data were obtained for live body weight and various carcass parts. Coefficients of variation of abdominal fat (g and g/100 g body weight) were above 30%. Coefficients of variation of the weights of muscular and skeletal parts were much lower (about 10%) and were further reduced when calculated per 100 g body weight. Heritability of abdominal fat was higher (.82) than that of live body weight (.55) and parts: breast (.55), thighs (.31), and drumsticks (.51). Phenotypic and genetic correlations between each of the heavier parts (breast, thighs, and drumsticks) and body weight were over .8; for smaller parts (legs, wings, etc.) correlations (.49 to .79) were lower. Abdominal fat showed the lowest correlation (.26 to .36) with body weight. The genetic correlations seemed free of the part-whole relationship. Simultaneous selections for live body weight and for breast weight, or against abdominal fat, were simulated using "independent culling levels". The theoretical calculations showed that adding breast weight as a selection criterion had no advantage over selection for body weight alone due to the high genetic correlation between the two traits. However, simultaneous selection for body weight and against abdominal fat, using optimum combination of culling, was economically superior to selection for body weight alone. The advantage of this two-trait selection depends on the correlation between the traits and their relative values.

Metabolic and anatomical adaptations of heavy-bodied chicks to intermittent feeding. I. Food intake, growth rate, organ weight, and body composition.

Chicks of a heavy-bodied strain were deprived of food on alternate days from 14 to 83 days of age. Relative food intake was depressed by intermittent feeding to 25 days of age, after which the deprived chicks resumed the relative intake of the ad libitum-fed controls, i.e., the relative intake on repletion day was twice that of the control chicks. Following an adaptation period of 2 weeks, the relative growth rate of the intermittently fed chicks exceeded that of the control group, the excessive growth being due to an increase on the day of repletion which was more than twice that of the control birds. Body fat concentration was depressed by intermittent feeding throughout the experimental period. Although, in ad libitum-fed chicks, periodical deposition of body protein and fat was parallel throughout the experimental period, in the treated chicks, protein deposition prevailed initially and fat deposition prevailed at the end of the experimental period. Intermittent feeding was accompanied by a consistent increase in the relative weight of the liver, pancreas, and gastrointestinal tract, including the small intestine. The differences in food intake, growth, body composition, and gastro-intestinal tract between heavy- and light-breed chicks exposed to intermittent feeding are discussed.

Effect of grain particle size on performance. 2. Grain texture interactions.

Diets were prepared with corn, wheat, or sorghum ground in a hammer mill and sieved to obtain coarse, medium, and fine particle size fractions. Their effect on broiler performance from hatch to 7 d and from 7 to 21 d of age was studied. The effect of particle size on the size and pH of the gastrointestinal organs was also determined. The three textures obtained for each grain were uniform in geometric mean diameter (GMD) and geometric standard deviation (GSD). Grain by texture interactions were not significant. Independent of grain source, the best performance was obtained with diets prepared from the medium texture. In these diets, the GMD of the grains varied from 1.13 to 1.23 mm and the GSD from 1.19 to 1.35. The fine fraction (GMD .57 to .67 mm) resulted in the lowest performance and that resulting from the coarse fraction (GMD 2.01 to 2.10 mm) was intermediate. At 7 and 21 d of age, gizzard weight and content were positively related to particle size. At the age of 21 d, duodenum weight and content was highest in chicks fed the fine diets. The pH of the gizzard content decreased with increasing grain particle size, whereas that of the small intestinal content increased. Some grain effects were also observed on the gastrointestinal tract. Gizzard weight was greatest in the cornfed birds. Wheat-fed chicks had the heavier intestines and contents. After overnight feed deprivation, feed consumption by 7-d-old chicks was related to the particle size during the first 2 h of refeeding, with greater intake of medium and coarse grains.

Effects of dietary protein under high ambient temperature on body weight, breast meat yield, and abdominal fat deposition of broiler stocks differing in growth rate and fatness.

The effect of dietary protein on growth, feed intake and efficiency, abdominal fat deposition, and breast meat yield was investigated in broiler males from a commercial stock (WI) and from experimental stocks selected for low (LF) or high (HF) abdominal fat. All birds were kept at constant high ambient temperature (32 C) and were provided with low- (LP) or high-protein (HP) diets from hatch until 8 wk of age (Experiment 1) or from 4 to 8 wk of age (Experiment 2). In both experiments, HP diet significantly increased 4- to 8-wk BW gain in the LF and HF stocks but reduced it in the WI stock as compared with the LP diet. Abdominal fat, as percentage of BW, was almost twofold higher in the HF birds than in the LF ones, with WI mean being intermediate. In contrast to the HF and WI birds, in which abdominal fat decreased with increased protein intake, abdominal fat was not affected by dietary protein in the LF stock. The HP diet substantially increased breast meat yield in LF birds but not in the WI birds, with HF birds exhibiting intermediate increase in breast meat weight. It was concluded that birds of varied inherent growth rate and tendencies toward protein and fat deposition respond differently to dietary protein level under heat stress.

Nutritional aspects of hydrogenated and regular soybean oil added to diets of broiler chickens.

The objective of the present study was to evaluate the effect of degree of saturation of fat incorporated into broiler diets on performance and body fatty acid (FA) profile. The various degrees of saturation were achieved by using regular soybean oil (SO) and hydrogenated soybean oil (HSO), mixed at different proportions. The work was carried out on commercial broilers (Experiment 1) and on lines of chickens divergently selected for high (HF) or low (LF) abdominal fat (Experiment 2). Daily BW gain and gain:feed ratio increased and the amount of feed intake decreased as the dietary fat saturation decreased. Digestibility of total fat and of each of the FA was lowest in the HSO group and reached maximal values when 23% or more of the added oil was SO. The AMEn values of the diets were almost parallel to fat digestibility. The performance of the HF and LF chickens was affected by the degree of saturation similarly to that observed for the commercial stock. The degree of dietary fat saturation had very little effect on saturated FA (C16:0 and C18:0) in body lipids, reduced the level of monoenoic FA (C16:1 and C18:1), and raised that of polyunsaturated FA (PUFA) (C18:2, C18:3, and C20:4). Monoenoic FA were higher, whereas PUFA were lower in the HF than in the LF line. The improved AMEn in diets containing unsaturated fat is probably due to higher fat digestibility, direct deposition of PUFA in body lipids, and lower lipogenesis, associated with lower heat production.

Organ growth and digestive enzyme levels to fifteen days of age in lines of chickens differing in body weight.

Weights of internal organs and levels of digestive enzymes were obtained through the first 15 days posthatch for cockerels from three lines of chickens known to differ greatly in body weight. On Day 15 body weights from the fastest growing line were eight times greater than those from the slowest growing line. Differences among lines were found for weights at hatching and for growth patterns (both absolute and relative to body weight) of the vitelline residue, heart, lungs, liver, pancreas, crop, proventriculus, gizzard, and segments of the small intestine. Line differences were also evident for levels of trypsin, chymotrypsin, and amylase in the pancreas and contents of the small intestine. Ranking of lines for these traits varied with age. In all lines weights of the small intestine, liver, and pancreas increased relatively more than did total body weight during the 1st wk posthatch, after which the relationship reversed.

Growth-associated traits in parental and F1 populations of chickens under different feeding programs. 1. Ad libitum feeding.

Two experiments were conducted to compare body composition, plasma concentrations of glucose, lipid and protein, gastrointestinal tract (GIT) morphology, and digestive enzyme activities among populations of chickens exhibiting wide differences in growth. In the first experiment, males from a high weight (HW) line, a low weight (LW) line, and crosses between the lines (HL) were examined. In the second experiment, the same high weight (HW') line, a White Leghorn (LEG) line and their crosses (HLEG) were compared. In both experiments, comparisons were made at both 25 and 61 days of age. The HW chicks were heavier and had larger breasts and longer shanks than the LW or LEG chicks. Although the crosses (HL, HLEG) exhibited values for these traits intermediate to those of the parental lines, HLEG chicks tended to resemble one of the parental lines more closely than did the HL chicks. Differences among all mating combinations were significant for body fat, but the crosses (HLEG, HL) tended to more closely resemble their HW parental line. The HW chicks had significantly higher concentrations of glucose, lipid, and protein in plasma at 25 but not 61 days of age. No differences in glucose, lipid, or protein concentrations in plasma were observed in the second experiment. When expressed as a percentage of body weight, LW and LEG chicks tended to have larger GIT than HW chicks, whereas crosses more closely resembled the HW line. Although significant differences in digestive enzyme activities were obtained, these differences were generally associated with differences in body weight. It was concluded that genetic variation in the traits examined was dependent on both population and age.

Growth-associated traits in parental and F1 populations of chickens under different feeding programs. 2. Ad libitum and intermittent feeding.

Growth traits and digestive enzyme activities were compared in parental lines and F1 crosses under ad libitum and alternate-day feeding. Responses to the feeding regimens were, in general, dependent on the background genome and age. Population by feeding regimen interactions were more prevalent for growth traits than for enzymatic activities. Although chickens adapted morphologically and physiologically to the particular feeding regimen to which they were exposed, the degree of adaptation was population dependent. Moreover, a line of White Leghorns differed considerably in response compared to a line of White Rocks selected for low body weight, demonstrating that weight is primarily a result of metabolic and behavioral processes rather than the determiner of those processes.

Intubation of weight-selected chicks with soybean oil or residual yolk: effect on early growth and development.

Experiments were conducted to study the role of residual yolk on growth and development of chicks during the 1st wk after hatch. Surgical removal of the yolk sac at hatch reduced early body weight gains. Intubating chicks with a mixture of soybean meal and soybean oil or with residual yolk obtained from chicks at hatch increased body weights and enhanced development of the liver and pancreas. Whereas intubation with residual yolk reduced absorption of yolk sac contents, absorption was similar for chicks that consumed mash ad libitum or were intubated with the soybean meal-soybean oil diet. After cessation of yolk intubation, absorption of residual yolk resumed. Removal of the yolk sac decreased amylase and lipase activity in the pancreas. In the intestinal chyme, activity of amylase, trypsin, and chymotrypsin was reduced by yolk sac removal. Intubation with yolk increased enzyme activity (amylase excepted) in the pancreas or intestinal chyme only in chicks that had their yolk sacs removed. There was evidence that contents of the yolk sac did not enter the intestine via the yolk stalk, but were absorbed directly via the blood.