Calcified cerebral emboli.

Intracranial calcifications may represent calcified cerebral emboli. Calcified emboli may be overlooked even though cerebral CT is widely used as a stroke assessment. We report 4 cases of calcified cerebral emboli and demonstrate the value of CT in the diagnosis and temporal evaluation of such emboli.

Diffusion-weighted imaging findings in Balo concentric sclerosis.

Balo concentric sclerosis is a rare demyelinating disease. Pathognomonic features have been previously described. Diffusion-wighted imaging findings have not been previously described in Balo concentric sclerosis. We describe the diffusion-weighted imaging findings in a 45-year-old lady with Balo concentric sclerosis. Diffusion-weighted imaging offers insight into the possible pathophysiology of this rare disease.

Adult xanthogranulomatous disease of the orbit and ocular adnexa: new immunohistochemical findings and clinical review.

BACKGROUND/AIMS: Adult xanthogranulomatous disease involving the ocular tissues is rare and poorly understood. Adult onset xanthogranuloma (AOX), adult onset asthma and periocular xanthogranuloma (AAPOX), necrobiotic xanthogranuloma (NBX), and Erdheim-Chester disease (ECD) are the four syndromes within this disorder, which is diagnosed by characteristic histopathology. Experience with eight cases prompted a multi-institutional effort to study the histopathology, immunohistochemistry, clinical findings, and systemic associations in this disorder. METHODS: 22 cases, including histopathological slides, were compiled. Published reports were identified by an English language Medline search (1966-2005) and review of reference citations. Each case in this series and the literature was classified as one of four syndromes and then analysed for age onset, sex, skin xanthoma, orbital location, immune dysfunction, internal organ and bone lesions, treatment, and outcome. The histopathology in each of these cases was reviewed by two pathologists. Immunhistochemical stains (CD3, CD4, CD8, L26) were performed in 14 cases where unstained slides were available. RESULTS: 137 cases were compiled. There was no sex or age difference between syndromes. AOX, AAPOX, NBX affect the anterior orbit, ECD tends to be diffuse and intraconal. Skin lesions are found in all the syndromes. Immune dysfunction was noted in all cases of AAPOX and NBX; 11% of NBX and all ECD patients had internal organ disease. Treatment included surgery, corticosteroids, other chemotherapeutic agents, radiotherapy, and combinations of these. No AOX or AAPOX deaths occurred; 66% of ECD patients died. All 22 cases had xanthoma cells; most had Touton giant cells. Lymphocytes were present in all cases and occurred as aggregates (mostly in AAPOX) or diffuse populations mixed with fibroblasts (mostly in ECD). Immunohistochemistry revealed the majority of these to be CD8+. Necrosis was most marked in NBX. CONCLUSION: Adult xanthogranuloma of the orbit is rare, making prospective evaluation or meta-analysis impossible. The best treatment is unknown but seems to be with multiagent chemotherapy guided by histopathological, immunohistochemical, and systemic findings.

Localised invasive sino-orbital aspergillosis: characteristic features.

BACKGROUND/AIM: To describe the characteristic constellation of historical, clinical, radiographic, and histopathological findings of localised invasive sino-orbital aspergillosis based on the authors' recent experience of four consecutive cases presenting over a 6 month period. Treatment and outcome are reviewed. METHODS: A case series of four patients with review of the English language literature. RESULTS: There have been 17 reported cases of invasive sino-orbital aspergillosis in healthy individuals over the past 33 years. The authors report four patients who presented during a 6 month period with persistent and significant pain followed by progressive ophthalmic signs-clinical histories reflecting the literature. Similar imaging findings were also noted: focal hypodense areas within apical infiltrates on contrasted computed tomography correspond to abscesses seen at surgery, and sinus obliteration or involvement of the adjacent sinus lining was noted on magnetic resonance imaging. Bone erosion (often focal) was also seen. There is frequently a delay in making the correct diagnosis, and often disease progression occurs despite treatment. CONCLUSIONS: The authors encountered four cases of invasive sino-orbital aspergillosis, three of which occurred in otherwise healthy individuals. The clinician must be aware of the characteristic presentation so that earlier diagnosis, management, and improved outcomes can be achieved.

Heritability of body length and measures of body density and their relationship to backfat thickness and loin muscle area in swine.

The objective of this study was to estimate heritability for body length (LEN) at the end of performance testing and to estimate genetic correlations with backfat (BF) thickness and loin muscle area (LMA) in Landrace, Yorkshire, Duroc, and Hampshire breeds of swine. Also examined were two measures of body density involving body length and weight and their relationships to backfat and loin muscle area. Data consisted of performance test records collected in a commercial swine operation from 1992 to 1999. Boars from 60% of the litters were culled at weaning based on a maternal breeding value of the dam. Remaining boars and all females were grown to 100 d of age (15,594, 55,497, 12,267, and 9,782 Landrace, Yorkshire, Duroc, and Hampshire pigs, respectively). At this time, all pigs were weighed (WT100) and selected for performance testing based on a combination of maternal and performance indexes, which differed by breed. All pigs were weighed at the end of the 77 d performance test (WT177) when BF, LMA, and LEN were measured. Two measures of body density involving length were calculated: Body mass index (BMI) = WT177/LEN2 and body density (DENSITY) = WT177/LEN. For each breed, genetic parameters were estimated using an animal model with random litter effects and multiple-trait REML procedures. A series of three-trait models including WT100 and combinations of two other traits in each analysis was conducted. Fixed effects included contemporary group and age as a covariate. Average estimates of heritability were 0.16 to 0.32 for LEN (unadjusted for WT177), 0.12 to 0.26 for LEN (adjusted for WT177), 0.23 to 0.33 for DENSITY, and 0.16 to 0.25 for BMI. Genetic correlations between LEN and LMA were low. Genetic correlations between LEN (unadjusted for WT177) and BF were 0.10 to 0.41. Adjusting LEN for WT177 gave correlations of 0.11 for Landrace and Hampshire and negative correlations (-0.06 and -0.19, respectively) for Yorkshire and Duroc. Genetic correlations between LMA and DENSITY and between LMA and BMI were comparable and ranged from 0.44 to 0.54. Genetic correlations between BF and DENSITY were slightly higher (0.53 to 0.68) than those between BF and BMI (0.37 to 0.67). In these data, not much relationship between BF and body length at a constant weight and age was found. There was a negative relationship between LMA and LEN at a constant weight and age, implying that longer pigs had smaller LMA.

Maternal effects on traits measured during postweaning performance test of swine from four breeds.

The objective of this study was to investigate the importance of maternal genetic effects on postweaning performance traits of Yorkshire, Landrace, Duroc, and Hampshire breeds of swine. Data consisted of performance test records collected in a commercial swine operation from 1992 to 1999. Boars from 60% of the litters were culled at weaning based on a combination of maternal and performance indexes that differed by breed. Remaining boars and all females were grown to 100 d of age. At this time all pigs were weighed (WT100) and selected for testing using recalculated breed-specific indexes (n = 15,594, 55,497, 12,267, and 9,782 for Landrace, Yorkshire, Duroc, and Hampshire, respectively). All pigs were weighed at the end of the 77-d test, and backfat (BF) and loin eye area (LEA) were measured over the 12th rib by ultrasound. Average daily feed intake was calculated for boars, and ADG was calculated for all animals. Genetic parameters were estimated for each breed and trait using multiple-trait DFREML procedures. Fixed effects were contemporary groups and either initial or final test age as a covariate. Four models were examined. Model 1 included only the additive genetic effect of the animal. Model 2 added the common litter environmental effect; Model 3 added the maternal genetic value assumed to be uncorrelated with additive genetic effects. Model 4 was the same as Model 3 with additive and maternal genetic effects assumed to be correlated. All models were two-trait models with WT100 as the second trait. Ratios of likelihoods were used to compare models. Maternal effects were important (P < 0.05) for WT100, ADG, ADFI, LEA, and BF in Landrace; for WT100, ADG, LEA, and BF in Yorkshire; for WT100 and ADG in Duroc, and for WT100 in Hampshire. Estimates of heritabilities for direct additive effects using the appropriate model for ADG, ADFI, LEA, and BF were 0.28, 0.34, 0.48, and 0.63 for Landrace; 0.26, 0.31, 0.39, and 0.65 for Yorkshire; 0.14, 0.20, 0.26, and 0.35 for Duroc; and 0.17, 0.23, 0.25, and 0.31 for Hampshire, respectively. Heritability estimates for maternal genetic effects for ADG, ADFI, LEA, and BF were 0.02, 0.05, 0.06, and 0.07 for Landrace and 0.02, 0, 0.04, and 0.06 for Yorkshire, respectively. They were zero for all traits except ADG (0.03) in Duroc and for all traits in Hampshire. Maternal effects may need to be considered in genetic evaluation of performance traits in some breeds of swine.

Baló's concentric sclerosis: surviving normal myelin in a patient with a relapsing-remitting dinical course.

Baló's concentric sclerosis is a demyelinating disorder in which bands of demyelination alternate with concentric bands of myelin preservation. The pathogenesis of the lesion is unknown. Previous reports using modern histopathologic techniques have shown the bands of myelin preservation to be comprised of remyelinated or partially demyelinated myelin. Here we report a case of Baló's concentric sclerosis in a 24-year-old East Indian patient with a previous history of relapsing-remitting multiple sclerosis (MS). Pathologically, the bands of myelin preservation showed myelin sheaths of normal thickness, with focal areas of demyelination. The findings, taken together with those of previously reported cases, suggest that Baló's concentric sclerosis is a variant of MS, and the concentric lesion may be an intermediary form in evolution of a chronic active MS plaque. The pathogenesis of this concentric lesion may be explained by periodic suppression of demyelination in the rapidly expanding border, allowing remyelination or only transient incomplete demyelination to occur.

A prospective randomized comparison of CT and MRI pre-operative localization for pallidotomy.

OBJECTIVE: During the pallidotomy procedure, is pre-operative localization with MRI more accurate than CT and does it result in a significant difference in surgical outcome? METHODS: Twenty-four Parkinson's Disease patients received a unilateral pallidotomy for their motor symptoms. Dyskinesia was scored pre- and six weeks postoperatively. All patients had a pre-operative CT scan and MRI to calculate the target co-ordinates. Patients were then randomly selected to proceed with either the CT or MRI coordinates. The final position for the lesion was determined with intraoperative macrostimulation and impedance measurements. The percentage improvement of dyskinesia was noted for each patient and the two groups compared by the Mann-Whitney test. The distance from the final target to the MRI and CT pre-operative co-ordinates were calculated for each patient. The mean distance for each modality was then compared by Student's t-test. The number of electrode repositionings was also recorded for each patient and the two groups compared by the nonparametric Mann-Whitney test. RESULTS: Although the MRI co-ordinates were significantly (p<0.023) closer to the final target, this did not translate into a significant reduction in electrode repositionings. There was no significant difference in the improvement in dyskinesia between the two groups. CONCLUSIONS: The pre-operative MRI co-ordinates were significantly (p=0.023) closer to the final target than those from the CT. The potential advantages and disadvantages of both imaging modalities are reviewed. There was no significant difference in surgical outcome using either MRI or CT for pre-operative localization in pallidotomy.

Genetic parameters for production traits and measures of residual feed intake in large white swine.

The purpose of this study was to estimate genetic parameters for ADG, backfat thickness and loin eye area (LEA), and measures of feed intake and efficiency for purebred Large White boars born from 1990 to 1997. Boars from 60% of the litters were culled at weaning based on a maternal breeding value (index) of the dam, and remaining boars (n = 26,706) were grown to 100 d of age. Selection of boars for individual pen testing was based on a combination of growth and maternal indices. Boars were fed a corn-soybean meal diet that was 1.14% lysine, 19% protein, and 3,344 kcal/kg ME for approximately 77 d. Boars were weighed at the beginning and end of the test, and feed intake was recorded. Daily feed intake (DFI), ADG, and feed:gain ratio (FG) were computed. Four measures of residual feed intake (RFI) were estimated as the difference between actual feed intake and that predicted from models that included 1) initial test age and weight and test ADG (RFI1); 2) initial test age and weight, test ADG, and backfat (RFI2); 3) initial test age and weight, test ADG, and LEA (RFI3); and 4) initial test age and weight, test ADG, backfat, and LEA (RFI4). Genetic parameters were estimated using an animal model and single- or multiple-trait DFREML procedures. Models included fixed effects of contemporary groups and initial test age as a covariate and random animal and litter effects. Heritability estimates for test ADG, DFI, FG, backfat, LEA, RFI1, RFI2, RFI3, and RFI4 were .24, .23, .16, .36, .24, .17, .11, .15, and .10, respectively. Genetic correlations between ADG and backfat, ADG and LEA, ADG and DFI, and ADG and FG were .37, .36, .82, and -.32, respectively. Genetic correlations between ADG and measures of residual feed intake ranged from .11 to .18. Genetic correlations of backfat with LEA, DFI, and FG were -.27, .64, and .40, respectively. Genetic correlations of backfat with RFI measures were higher when backfat was not included in the estimation of RFI. Genetic correlations for LEA with DFI and FG were 0 and -.52, respectively. Genetic correlations for LEA with RFI measures were all negative and ranged from -.31 to -.51. Genetic correlations indicate that selection for reduced RFI could be made without adversely affecting ADG. Backfat should also decrease, and LEA should increase. The amount of change in backfat or LEA would depend on the measure of RFI used.

Pyrimidine thioethers: a novel class of HIV-1 reverse transcriptase inhibitors with activity against BHAP-resistant HIV.

A series of pyrimidine thioethers was synthesized and evaluated for inhibitory properties against wild-type HIV-1 reverse transcriptase (RT) and an RT carrying the resistance-conferring mutation P236L. Modifications of both the pyrimidine and the functionality attached through the thioether yielded several analogues, which demonstrated activity against both enzyme types, with IC50 values as low as 190 nM against wild-type and 66 nM against P236L RT. Evaluation of a select number of pyrimidine thioethers in cell culture showed that these compounds have excellent activity against HIV-1IIIB-WT and retain good activity against a laboratory-derived HIV-1MF delavirdine-resistant variant.

Anti-inflammatory/antiarthritic ketonic bisphosphonic acid esters.

Bisphosphonate ester 2 is an inhibitor of inflammation, but is devoid of antiarthritic effects. SAR studies on a series of related bisphosphonate esters resulted in compounds 6e, 6i, 6j, and 6m, which exhibited excellent inhibition of an arthritis model, in addition to potent anti-inflammatory effects.

Bisphosphonates: a review of their novel anti-inflammatory properties and potential for the treatment of rheumatoid arthritis.

Bisphosphonates (BP) are synthetic pyrophosphates with a stable P-C-P bond replacing the more labile P-O-P bond. This structural class has been used extensively for the treatment of bone diseases, such as osteoporosis and hypercalcemia due to the propensity of BP to bind mineralized tissues and prevent bone resorption. Rheumatoid arthritis (RA) is characterized by chronic inflammatory synovitis, pannus tissue formation and erosion of bone and cartilage, which is a major, disabling, pathogenic feature poorly managed with existing disease modifying anti-rheumatic drugs (DMARDs). A few investigators have used BP in combination with anti-arthritic therapy to treat the bone erosion component of RA, reports of which are mainly anecdotal. We review data suggesting that BP possess novel anti-inflammatory properties which may also be of benefit for the treatment of the chronic inflammatory component of RA, thus modifying the subsequent destructive disease process by mechanisms unrelated to direct inhibition of bone resorption. The rationale for pursuing this therapeutic approach to demonstrate BP anti-inflammatory activity will be reviewed. The subsequent design and synthesis of new BP chemical entities and their altered pharmacokinetic properties will also be discussed.

Circulating insulin-like growth factor I, insulin-like growth factor binding proteins, growth hormone, and resumption of estrus in postpartum cows subjected to dietary energy restriction.

The objective of this study was to determine whether serum concentrations of growth hormone (GH), IGF-I, IGF binding proteins (IGFBP), and glucose at wk 2 and 10 postpartum were associated with the ability of postpartum beef cows to resume cycling when maintained on a limited nutrient environment. Cows (n = 29) were individually fed either 130 or 170 kcal ME x BW-75 x d-1 during nonlactation and 170 or 210 kcal ME x BW-75 x d-1 during lactation for an average of 4.1 yr before sample collection. The proportion of cows that resumed estrus within 20 wk after parturition was less (P < .05) at the lower feeding rate (5 of 14) than at the higher feeding rate (11 of 15). Concentrations of IGF-I increased from wk 2 to 10 in cows that resumed cycling but not in cows that remained anestrous and were less (P < .05) at wk 2 and 10 in cows that remained anestrous compared to cows that resumed cycling. Circulating amounts of IGFBP-2 at wk 2 were greater (P < .05) and IGFBP-3 concentrations were lower (P < .05) in cows that remained anestrous compared to cows that resumed cycling. Cows on the lower feeding rate that did not cycle had lower body condition scores and greater concentrations of GH compared (P < .05) to other cows. At the higher feeding rate, body condition score and concentrations of GH did not differ between cows that did or did not resume cycling. Circulating concentrations of IGF-I and IGFBP-2 and -3 at wk 2 postpartum were indicators of the capacity of energy-restricted cattle to resume cycling after parturition.

In vivo measurement of T2 distributions and water contents in normal human brain.

Using a 32-echo imaging pulse sequence, T2 relaxation decay curves were acquired from five white- and six gray-matter brain structures outlined in 12 normal volunteers. The water contents of white and gray matter were 0.71 (0.01) and 0.83 (0.03) g/ml, respectively. All white-matter structures had significantly higher myelin water percentages (signal percentage with T2 between 10 and 50 ms) than all gray-matter structures. The range in geometric mean T2 of the main peak for both white and gray matter was from 70 to 86 ms. T2 distributions from the posterior internal capsules and splenium of the corpus callosum were significantly wider (width is related to water environment inhomogeneity) than those from any other white- or gray-matter structures. Thus, quantitative measurement and analysis of T2 relaxation reveals differences in brain tissue water environments not discernible on conventional MR images. These differences may make short T2 components reliable markers for normal myelin.

Carbonyl-containing bisphosphonate esters as novel antiinflammatory and antiarthritic agents.

A study of the decomposition of the pyrazoline bisphosphonate ester 2 identified 3 as the sole bisphosphonate component. Evaluation in a delayed-type hypersensitivity granuloma model of chronic inflammation in mice (DTH-GRA) showed 3 to be a potent inhibitor of granuloma formation (sc, 10 mg/kg, 45%), but in a murine model of antigen-induced arthritis (AIA), no significant inhibition was observed. As a result, new ketonic bisphosphonate tetraethyl esters were synthesized from vinylidenebisphosphonic acid tetraethyl ester 4 and activated carbonyl compounds in 13-84% yield. 6 significantly inhibited the pathology of both the DTH-GRA (sc, 25 mg/kg, 45%) and AIA models (sc, 25 mg/kg, 55%). Other compounds in the series were not as potent. Our results show that bisphosphonate ester 6 can inhibit the chronic inflammatory response associated with cutaneous granuloma formation and erosive arthritis.

Demonstration of novel anti-arthritic and anti-inflammatory effects of diphosphonates.

Diphosphonates (DP) are synthetic pyrophosphates with a P-C-P backbone and are predominantly used for the treatment of bone diseases. Several DP have also been shown to exert significant antiarthritic effects in the rat adjuvant-induced polyarthritis model; however, there is no direct evidence for the anti-inflammatory effects of these compounds. We therefore tested the effects of dichloromethylene diphosphonate on delayed-type hypersensitivity granuloma elicited by s.c. implantation of antigen-soaked hydroxyapatite disks in antigen-sensitized mice. Dichloromethylene diphosphonate induced a dose-related inhibition of the delayed-type hypersensitivity granuloma response (38-64% at 25-100 mg/kg/day s.c. or p.o.); novel DP analogs, U-81581, U-82579 and U-84849 were also effective in the same dose range. In contrast, all DP failed to suppress 24-hr delayed-type hypersensitivity paw edema in mice. In addition to rat adjuvant-induced polyarthritis, mouse antigen-induced erosive arthritis was also significantly suppressed by s.c. administration of all four DP. Toxicity was minimal for each DP (> 600 mg/kg p.o. or s.c.). We conclude that DP represent a novel class of anti-inflammatory agents with excellent therapeutic potential for chronic inflammatory diseases including rheumatoid arthritis.

Radiotherapy in the management of thyroid orbitopathy. Computed tomography and clinical outcomes.

OBJECTIVE: We investigated the long-term outcome of patients with thyroid orbitopathy treated with orbital radiotherapy using quantitative clinical measurements and orbital computed tomographic morphometric changes. DESIGN: Patients who had undergone orbital radiotherapy for thyroid orbitopathy at least 1 year previously were retrospectively recalled for follow-up examination and computed tomography. Controls were patients with similar disease activity but who had not undergone radiotherapy. SETTING: Subspecialty clinic in a university teaching hospital. PATIENTS: Twenty-one patients (42 orbits) who underwent radiotherapy and six clinically comparable patients who had not undergone radiotherapy (12 orbits). INTERVENTION: Standardized, super-voltage, orbital radiotherapy. MEASUREMENTS: Five clinical indexes of orbitopathy and six computed tomographic indexes were examined for interval changes. RESULTS: The orbital computed tomographic muscle-diameter index enlargement ratio did not change in either group (radiotherapy group, 1.54 to 1.51, not significant; nonradiotherapy group, 1.37 to 1.36, not significant). The mean (+/- SEM) number of muscles with low-density areas increased in both groups (radiotherapy group, 1.1 [+/- 1.9] muscles per orbit; P < .001). Soft-tissue signs improved significantly with lesser improvements in extraocular muscle function in both groups. Proptosis, visual acuity, and intraocular pressure rise on upgaze did not improve significantly in either group. CONCLUSIONS: No changes in muscle size measured with computed tomography were found in either patients undergoing radiotherapy or patients not undergoing radiotherapy after long-term follow-up. Clinical indexes of thyroid orbitopathy, especially soft-tissue signs, improved on follow-up, but this was not influenced by the method of treatment.

Simulated effects of culling ewes for age and failure to conceive on biological efficiency of an annual lambing production system.

A deterministic computer simulation model was used to estimate the effects of different culling strategies for nonconception and age on the biological efficiency of an annual lambing system. Interaction among culling strategy and genotype for system efficiency was estimated by also varying ewe genetic potentials for fertility, precocity of fertility, and litter size. Biological efficiency was defined as grams of empty body weight equivalent value of market lamb, cull ewe, and wool output per kilogram input of TDN. Pure breeding with random selection of intraflock replacement ewe lambs was assumed. Sheep were fed to maintain normal weight. Maximum allowable ewe age (i.e., time at culling for age) was varied from 2 to 10 yr. The four strategies of culling for nonconception that were simulated ranged from no removal for nonconception to removal of all nonpregnant ewes 15 wk after exposure. During calculation of lamb empty body weight equivalent, relative values per kilogram of output for market lambs, cull ewes, and clean wool were assumed to be 1 to .33 to 2.04 for most simulation runs. In addition, relative value of cull ewes was varied to .01, .16, .50, or .99 for some simulations. The effect of strategy for removal of nonconceiving ewes on system efficiency depended on maximum ewe age and genotype. In general, if relative value per kilogram of cull ewes to market lambs was < or = .50, ewes should be allowed to produce through 4 or 5 yr of age and then be salvaged. Unless salvage value of culled ewes approaches that of market lambs, ewe lambs should not be culled for failure to conceive.