Autoimmune limbic encephalitis in 39 patients: immunophenotypes and outcomes.

BACKGROUND: About 40% of patients with limbic encephalitis do not have detectable CNS antibodies. Some of these patients have immune-mediated limbic encephalitis, but their frequency is unknown. AIMS: (1) To determine the spectrum of limbic encephalitis identified on clinical grounds in a single institution, and compare it with that in patients referred for antibody analysis. (2) To correlate clinical outcomes with the cellular location of the autoantigens. METHODS: Prospective clinical case studies. Immunohistochemistry with rat brain, live hippocampal neurones, HeLa cells expressing Kv potassium channels and immunoblot. RESULTS: In 4 years, 17 patients were identified in the Hospital of the University of Pennsylvania, Philadelphia, USA, and the serum or CSF samples of 22 patients diagnosed elsewhere were also studied. 9 of our 17 (53%) patients had antibodies to known neuronal antigens (paraneoplastic or voltage gated potassium channels (VGKCs)) and 5 (29%) to novel cell-membrane antigens (nCMAg) typically expressed in the hippocampus and sometimes in the cerebellum. Considering the entire series, 19 of 39 (49%) patients had antibodies to known antigens, and 17 (44%) to nCMAg. Follow-up (2-48 months, median 19 months) was available for 35 patients. When compared with patients with antibodies to intraneuronal antigens, a significant association with response to treatment was found in those with antibodies to cell-membrane antigens in general (VGKC or nCMAg, p = 0.003) or to nCMAg (p = 0.006). CONCLUSIONS: (1) 82% of patients with limbic encephalitis prospectively identified on clinical grounds had CNS antibodies; (2) responsiveness to treatment is not limited to patients with VGKC antibodies; (3) in many patients (29% from a single institution), the autoantigens were unknown but were found to be highly enriched in neuronal cell membranes of the hippocampus; and (4) these antibodies are associated with a favourable outcome.

Orchiectomy for suspected microscopic tumor in patients with anti-Ma2-associated encephalitis.

OBJECTIVE: To report the presence of microscopic neoplasms of the testis in men with anti-Ma2-associated encephalitis (Ma2-encephalitis) and to discuss the clinical implications. METHODS: Orchiectomy specimens were examined using immunohistochemistry with Ma2 and Oct4 antibodies. RESULTS: Among 25 patients with Ma2-encephalitis younger than 50 years, 19 had germ-cell tumors, and 6 had no evidence of cancer. These 6 patients underwent orchiectomy because they fulfilled five criteria: 1) demonstration of anti-Ma2 antibodies in association with MRI or clinical features compatible with Ma2-encephalitis, 2) life-threatening or progressive neurologic deficits, 3) age < 50 years, 4) absence of other tumors, and 5) new testicular enlargement or risk factors for germ-cell tumors, mainly cryptorchidism or ultrasound evidence of testicular microcalcifications. All orchiectomy specimens showed intratubular-germ cell neoplasms unclassified type (IGCNU) and other abnormalities including microcalcifications, atrophy, fibrosis, inflammatory infiltrates, or hypospermatogenesis. Ma2 was expressed by neoplastic cells in three of three patients examined. Even though most patients had severe neurologic deficits at the time of orchiectomy (median progression of symptoms, 10 months), 4 had partial improvement and prolonged stabilization (8 to 84 months, median 22.5 months) and two did not improve after the procedure. CONCLUSIONS: In young men with Ma2-encephalitis, 1) the disorder should be attributed to a germ-cell neoplasm of the testis unless another Ma2-expressing tumor is found, 2) negative tumor markers, ultrasound, body CT, or PET do not exclude an intratubular germ-cell neoplasm of the testis, and 3) if no tumor is found, the presence of the five indicated criteria should prompt consideration of orchiectomy.

Stockpiled forage or limit-fed corn as alternatives to hay for gestating and lactating beef cows.

In Exp. 1, 31, 24, and 17 mature, pregnant Simmental x Angus cows (initial BW = 662.0 +/- 10.4 kg) in each of 3 yr were used to determine the efficacy of stockpiled orchardgrass, limit-fed corn, or ad libitum hay for maintaining cows in mid- to late gestation, respectively. In Exp. 2, 24 mature, pregnant crossbred cows (initial BW = 677.7 +/- 9.4 kg) per treatment in each of 3 yr were used to determine the efficacy of stockpiled orchardgrass, limit-fed corn, or ad libitum hay for maintaining cows in late gestation and early lactation, respectively. Each year, cows were assigned to treatment by BW. From November to February or from January to April, respectively, nutritional needs for mid- to late gestation (Exp. 1) or late gestation and early lactation (Exp. 2) were met either by 1) rotating cows on approximately 15.2 or 21.7 ha of predominantly orchardgrass pasture, set aside and fertilized in late August, 2) limit-feeding approximately 5.8 kg of whole shelled corn, 1.1 kg of a pelleted supplement, and 1.2 kg of hay daily, or 3) ad libitum feeding of round-baled hay. During extreme weather conditions, cows grazing stockpiled orchardgrass were limit-fed a grain-based diet. Postcalving weight (P < 0.10) was greatest for limit-fed cows in Exp. 1 and lowest for cows grazed on stockpiled orchardgrass; cows given ad libitum access to hay were intermediate in weight and did not differ from cows limit-fed or cows grazed on stockpiled orchardgrass (641.8, 657.4, and 634.0 kg, respectively). Calving date, calf birth and weaning weight, and conception rate did not differ among treatments (P > 0.15) in Exp. 1. In Exp. 2, weight at weaning did not differ among treatments (P > 0.17); however, postcalving weight (P < 0.01) was greatest for cows given ad libitum access to hay, intermediate for limit-fed cows, and lowest for cows grazed on stockpiled orchardgrass (674.8, 652.4, and 624.5 kg). Body condition score at any time point did not differ among treatments (P > 0.38), nor did calving date, calf birth and weaning weights, and conception rate (P > 0.12). Because of the few differences in cow performance, selection of energy sources for beef cows can be made based on economics. The cost to feed a cow hay in early to mid-gestation was nearly double that of limit-feeding the corn-based diet or grazing stockpiled orchardgrass. Because of lower quality pastures, the cost to graze cows on stockpiled orchardgrass during late gestation and early lactation was not as cost effective as limit feeding a corn-based diet.

Effect of an accelerated finishing program on performance, carcass characteristics, and circulating insulin-like growth factor I concentration of early-weaned bulls and steers.

Sixty-three Angus x Simmental calves were allotted to a bull or a steer group based on sire, birth date, and birth weight to determine effects of castration status on performance, carcass characteristics, and circulating insulin-like growth factor I (IGF-I) concentrations in early-weaned cattle. At 75 d of age, calves in the steer group were castrated. Calves were not creep-fed prior to weaning. All calves were weaned and weighed at an average age of 115 d and transported by truck to the OARDC feedlot in Wooster, OH. Performance and carcass characteristics were measured in three phases. Phase 1 was from 115 to 200 d of age, phase 2 was from 201 to 277 d of age, and phase 3 was from 278 d of age to slaughter. Before implantation, four bulls and four steers were selected for serial slaughter and carcass evaluation. Steers were implanted with Synovex-C at 130 d of age and with Revalor-S at 200 and 277 d of age. Serum samples were collected from all calves on the day of implantation, 28 and 42 d after implantation, and at slaughter and analyzed for circulating IGF-I concentration. Bulls gained 9.7% faster (1.75 vs 1.60 kg/d; P < 0.01), consumed 25 kg more DM (521 vs 496 kg; P = 0.11), and were 3.3% more efficient (282 vs 273 g/kg, P < 0.10) than steers in phase 1. However, steers gained 10.5% faster (1.62 vs 1.46 kg/d; P < 0.02), consumed similar amounts of DM, and were 6.5% more efficient than bulls (214 vs 201 g/kg; P < 0.06) in phase 2. Overall gains and efficiency were similar between bulls and steers; however, bulls consumed 140 kg more DM (P < 0.05), were 27 kg heavier (P < 0.05), and had to stay in the feedlot 18 more days (P < 0.05) than steers to achieve a similar amount of fat thickness. Implanted steers had greater concentrations of circulating IGF-I than bulls (P < 0.01), and the pattern of IGF-I concentration over time was affected by castration status (castration status x time interaction; P < 0.01). Synovex-C had a lower impact on circulating IGF-I concentration (implant effect, P < 0.01) than either Revalor-S implant. Eighty-five percent of both bulls and steers had marbling scores sufficient to grade low Choice or better. Bulls achieved their target fat thickness later, increased muscle growth, and deposited fat more favorably than steers, possibly due to a gradual increase in IGF-I concentration as the testicles grew rather than the large fluctuations in IGF-I concentration observed in steers following implantation.

Effects of programmed growth rate and days fed on performance and carcass characteristics of feedlot steers.

Two experiments were conducted to investigate a feeding regimen in which a programmed amount of feed was offered daily to control growth rate of steers. In Exp. 1, steers (n = 107, 309 +/- 3 kg) were used to determine effects of offering ad libitum access to feed (AL) vs a programmed intake feeding regimen (PI) and the number of days steers were fed (168 vs 203) on performance and carcass characteristics. Steers in the programmed intake feeding regimen were fed to achieve a predicted gain of 1.13 kg/d for the first 78 kg of gain, 1.36 kg/d for the next 124 kg of gain, and were given ad libitum access to feed for the final 54 or 103 kg of gain before slaughter (for steers fed for 168 d or 203 d, respectively). Feed efficiency was greater (P < 0.02) for steers in the PI than for those in the AL feeding regimen (0.193 vs 0.183 kg gain/kg feed, respectively). From d 169 to 203, steers in the PI feeding regimen had greater (P < 0.06) ADG (1.60 vs 1.38 kg/d) and similar (P = 0.38) feed efficiency than steers in the AL regimen. In Exp. 2, steers (n = 96; 308 +/- 3 kg BW) were offered feed ad libitum throughout the experiment (AL) or were programmed to gain at a high (PI-H) or low (PI-L) growth rate. For the first 78 kg of gain, intake was restricted to achieve predicted gains of 1.13 kg/d (PI-L) or 1.25 kg/d (PI-H). For the next 124 kg of gain, intake was restricted to achieve predicted gains of 1.36 kg/d (PI-L) or 1.47 kg/d (PI-H). Feed was offered ad libitum for the final 58 kg of gain. Overall ADG was similar (P > 0.37) among feeding regimens despite lower DMI for the steers in the PI-L and PI-H feeding regimens than for those in the AL regimen. Feeding regimen did not affect (P < 0.22) carcass characteristics. Programmed intake feeding regimens sustained growth rate and feed efficiency for an extended period of time without detrimental effects on carcass characteristics.

Proportion of corn silage in diets of feedlot steers fed to achieve stepwise increases in growth.

Two experiments were conducted to investigate the effects of proportion of dietary corn silage during periods of feed restriction on performance of steers. In Exp. 1, Simmental x Angus steer calves (n = 107; initial BW = 273 +/- 3.8 kg) were allotted to 12 pens with eight or nine steers/pen and four pens/treatment. Periods of growth were 273 to 366 kg BW (Period 1), 367 to 501 kg BW (Period 2), and 502 to 564 kg BW (Period 3). In two of the dietary regimens, steers were given ad libitum access to feed throughout the experiment and were fed either a 15% corn silage diet in each period or an 85, 50, and 15% corn silage diet in Periods 1, 2, and 3; respectively. In the third feeding regimen, a programmed intake feeding regimen was used. Steers were fed a 15% corn silage diet in each period. However, feed intake was restricted to achieve a predicted gain of 1.13 kg/d in Period 1 and 1.36 kg/d in Period 2, and feed was offered for ad libitum consumption in Period 3. For the entire experiment, ADG was similar (P = 0.41) among treatments and feed efficiency was lower (P < 0.10) for steers in the corn silage regimen than for steers in the programmed intake and ad libitum regimens. In Exp. 2, Simmental x Angus steer calves (n = 106; initial BW = 233 +/- 2 kg) were allotted by BW to 12 pens (three pens/treatment) and fed in three periods similar to those described in Exp. 1. Four feeding regimens were investigated: 1) AL; steers were offered a 15% corn silage diet for ad libitum consumption in all three periods; 2) PI; DMI was programmed to achieve gains as described in Exp. 1; 3) CS-HLL; programmed intake as described above except diets contained 85, 15, and 15% corn silage in Periods 1, 2, and 3, respectively; and 4) CS-HIL; same feeding regimens as CS-HLL, except diets contained 85, 50, and 15% corn silage in Periods 1, 2, and 3, respectively. Steers were given ad libitum access to feed in Period 3. Overall ADG was lower (P < 0.05) for steers in the CS-HLL and CS-HIL feeding regimens than for steers in the AL and PI regimens; feed efficiency was greatest for steers in the PI regimen. Few effects of feeding regimen on carcass characteristics were observed.

Effects of dietary crude protein concentration during periods of feed restriction on performance, carcass characteristics, and skeletal muscle protein turnover in feedlot steers.

In Exp. 1, 36 individually penned steers (initial BW = 294 +/- 3.8 kg) were used to determine effects of dietary CP percentage and programming gain on performance and carcass characteristics. Steers were fed to achieve a predicted gain of 1.13 kg/d for the first 84 kg of gain and 1.36 kg/d for the next 124 kg of gain and were offered feed for ad libitum consumption for the final 58 kg of gain before slaughter. In these three phases of growth, steers were fed diets, sequentially, with the following CP percentages: HHH (16, 13.5, and 12.5%), LHH (9, 13.5, and 13%), or LLL (9, 9, and 9%). When predicted gain was 1.13 kg/d, ADG was greater (P < 0.01) for steers in the HHH (1.09 kg/d) vs LHH and LLL (0.83 kg/d) systems. When predicted gain was 1.36 kg/d, ADG and gain efficiency were greatest (P < 0.01) for steers in the LHH system. Overall ADG and gain efficiency were greater (P < 0.01) for steers in the HHH (1.46 kg/d, 0.194) and LHH systems (1.38 kg/d, 0.190), compared with steers in the LLL (1.21 kg/d and 0.166) system. Carcass fat thickness was lower for steers in the LHH (0.74 cm) system than for steers in the LLL system (1.09 cm). In Exp. 2, 18 individually penned steers (initial BW = 225 +/- 5.8 kg) were either offered a 13% CP diet for ad libitum intake (AL) throughout the 134-d experiment or fed a high- (16% CP; PI-HH) or low- (10% CP; PI-LH) CP diet and fed to achieve a predicted gain of 1.13 kg/d for the first 85 d of the experiment. Steers in the PI-HH and PI-LH feeding regimens were then offered a 13% CP diet for ad libitum consumption from d 86 to 134. Fractional protein accretion rate was greater (P < 0.01) for steers in the PI-HH and PI-LH feeding regimens than for steers in the AL regimen at d 92, 106, and 120. Fractional breakdown and synthesis rates were not affected (P = 0.63) by feeding regimen. Increased ADG and gain efficiency of steers during compensatory growth periods may in part be due to greater fractional accretion rates of skeletal muscle protein.

Effects of crude protein concentration in diets of feedlot steers fed to achieve stepwise increases in rate of gain.

Two experiments were conducted to determine supplemental CP requirements for feedlot steers prescription-fed to achieve stepwise increases in ADG during the feeding period. In Exp. 1, 106 steers (initial BW = 285.7 +/- 3.4 kg) were allotted to 12 pens. Treatments consisted of ad libitum consumption of a 12% CP diet throughout the experiment (AL12%), prescription intake of a 12% CP diet (PI12%), or prescription intake of high-CP diets (PIHCP). The PIHCP diets were formulated to provide the same grams of CP per day as the AL12% diet. Steers in the prescription intake feeding regimens were fed to gain 1.13 kg/d for the first 87 kg of gain and 1.36 kg/d for the next 134 kg of gain and were offered feed for ad libitum consumption for the final 52 kg of gain before slaughter at 559 kg. Overall ADG was lower (P < 0.05) for steers fed PI12% and PIHCP diets than for those fed the AL12% diet (1.48 and 1.50 vs 1.60 kg/d, respectively). Total DM intake was lower (P < 0.08) for steers fed the PI12% and PIHCP diets than for steers fed the AL12% diet (1,359, 1,370, and 1,421 kg, respectively). Dressing percentage, back-fat thickness, and quality grade were lower (P < 0.05) for steers fed the PI12% and PIHCP diets than for steers fed the AL12% diet. In Exp. 2, 142 steers (initial BW = 285.4 +/- 3.1 kg) were allotted to 16 pens. System 1 was ad libitum consumption of a 12% CP diet throughout the experiment. Steers in Systems 2, 3, 4, and 5 were subjected to the same prescription intake strategy as steers in Exp. 1. During the three phases of growth (1.13 kg/d, 1.36 kg/d, and ad libitum), steers were fed the following CP concentrations: System 2(12, 14, and 12%); System 3(12, 14, and 14%); System 4(12, 16, and 12%); and System 5(12, 16, and 14%). No differences (P > 0.06) in total steer performance, carcass characteristics, or carcass chemical composition were observed among systems. Increasing percentage of CP in diets of prescription-fed steers to provide the same daily intake of CP as steers consuming feed ad libitum was not beneficial.

Net flux of nutrients across splanchnic tissues in wethers consuming grasses of different sources and physical forms ad libitum.

Crossbred sheep (n 16, 8.5 months of age and 33 (SE 0.9) kg) were used in a 21 d experiment (2 x 2 factorial) to determine effects on net flux of nutrients across the portal-drained viscera (PDV) and liver of ad libitum consumption of bermudagrass (Cynodon dactylon; B) v. ryegrass (Lolium multiflorum)-wheat (Triticum aestivum; RW) hay, coarsely chopped (CC) or finely ground and pelleted (GP). Crude protein concentrations were 86, 81, 113 and 119 g/kg and neutral-detergent fibre concentrations were 710, 688, 654 and 672 g/kg (dry matter basis) for B-CC, B-GP, RW-CC and RW-GP respectively. Digestible energy intake (6.0, 9.6, 10.2 and 13.8 MJ/d) differed (P < 0.01) with grass source and form, and digestible N intake values were 4.4, 7.0, 8.4 and 14.1 (SEM 0.82) g/d for B-CC, B-GP, RW-CC and RW-GP diets respectively. Consumption of O2 by the PDV (118, 165, 144 and 155 mmol/h) and splanchnic bed (196, 273, 247 and 266 mmol/h for B-CC, B-GP, RW-CC and RW-GP respectively) was greater (P = 0.07) for GP than for CC. The ratio splanchnic heat energy production: digestible energy intake was greater (P = 0.06) for B than for RW (0.374, 0.300, 0.278 and 0.219 for B-CC, B-GP, RW-CC and RW-GP respectively). alpha-Amino-N release by the PDV (P < 0.01; 11.6, 12.8, 23.0 and 18.7 mmol/h) and uptake by the liver (P = 0.07; 15.2, 6.1, 17.0 and 19.3 mmol/h for B-CC, B-GP, RW-CC and RW-GP respectively) were greater for RW than for B. Release of NH3-N by the PDV was greater (P = 0.02) for CC than for GP (12.5, 6.2, 15.7 and 8.9 mmol/h), and hepatic urea-N release differed between grass sources (P = 0.03) and physical forms (P = 0.07; 22.6, 12.7, 31.4 and 24.8 mmol/h for B-CC, B-GP, RW-CC and RW-GP respectively). In conclusion, decrease in forage particle size elicited by grinding and pelleting did not affect the difference between grass sources in splanchnic tissue heat energy production relative to digestible energy intake.

Oxygen consumption by splanchnic tissues in wethers consuming ad libitum different proportions of bermudagrass and ryegrass-wheat.

Crossbred wethers (n = 18, 7.5 month of age and 31 +/- 0.8 kg) were used in a 23-day experiment to determine effects of ad libitum consumption of diets differing in proportions of coarsely chopped bermudagrass and ryegrass-wheat hay (0, 33, 67 and 100%) on oxygen consumption by splanchnic tissues. Bermudagrass and ryegrass-wheat were 9 and 13% CP and 78 and 71% NDF, respectively. Intake of dry matter (1.03, 0.92, 0.92 and 0.76 kg/d) and digestible energy (13.5, 10.7, 10.6 and 8.2 MJ/d for 0, 33, 67 and 100% bermudagrass, respectively) changed linearly and cubically (P < 0.05) as bermudagrass level increased. Consumption of oxygen by the portal-drained viscera tended to decrease linearly (P = 0.14) with increasing bermudagrass (182, 154, 156 and 137 mM/h), and hepatic oxygen consumption decreased linearly (P < 0.05) and changed cubically (P = 0.07; 150, 113, 116 and 103 mM/h for 0, 33, 67 and 100% bermudagrass, respectively). Splanchnic tissue energy consumption expressed as a percentage of digestible energy intake increased linearly (P = 0.08) with increasing bermudagrass (24.0, 27.6, 28.6 and 33.2% for 0, 33, 67 and 100% bermudagrass, respectively). In conclusion, the level rather than presence alone of different grass sources consumed ad libitum affected energy use by the splanchnic bed, and as a percentage of digestible energy intake splanchnic bed energy consumption increased with increasing dietary bermudagrass level and decreasing digestible energy intake.