Prospective evaluation of laparoscopic pancreatic biopsies in 11 healthy cats.

BACKGROUND: Definitive diagnosis of feline pancreatic disease is dependent on histologic examination of biopsies. HYPOTHESIS: Laparoscopic punch biopsy of the pancreas does not significantly affect pancreatic health or clinical status of healthy cats, and provides an adequate biopsy sample for histopathology. ANIMALS: Eleven healthy female domestic shorthair cats. METHODS: Effects of laparoscopic pancreatic visualization alone in 5 cats compared with laparoscopic pancreatic visualization and punch biopsy in 6 cats were studied. Temperature, pulse, and respiratory rate, physical examination, and daily caloric intake were evaluated for 1 week before and 1 week after the procedure. Pain scores (simple descriptive score and dynamic interactive visual assessment score) were evaluated hourly during the 1st 6 hours postprocedure. Complete blood cell counts, serum biochemical profiles, serum feline pancreatic lipase immunoreactivity, and urine specific gravity were evaluated before the procedure and at 6, 24, and 72 hours postprocedure. One month postprocedure, during sterilization, the pancreas was reassessed visually in all cats, and microscopically in the biopsy group. RESULTS: For all variables evaluated, there were no significant differences between biopsy and control cats. Re-evaluation of the pancreatic biopsy site 1 month later documented a normal tissue response to biopsy. The laparoscopic punch biopsy forceps provided high-quality pancreatic biopsy samples with an average size of 5 mm x 4 mm on 2-dimensional cut section. CONCLUSIONS AND CLINICAL IMPORTANCE: Laparoscopic pancreatic biopsy is a useful and safe technique in healthy cats.

Identification of link proteins in canine synovial cell cultures and canine articular cartilage.

Link proteins are glycoproteins in cartilage that are involved in the stabilization of aggregates of proteoglycans and hyaluronic acid. We have identified link proteins in synovial cell cultures form normal canine synovium using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, immunofluorescence, and immunolocation with specific antibodies by electrophoretic transfer. We have also found evidence for the synthesis of link proteins in these cultures by fluorography of radiolabeled synovial cell extracts. We have identified a 70,000 mol-wt protein in canine synovial cell culture extracts that has antigenic cross-reactivity with the 48,000-mol-wt link protein. Three link proteins were identified in normal canine articular cartilage. These results indicate that link proteins are more widely distributed in connective tissues than previously recognized and may have biological functions other than aggregate stabilization.

Pregnancy and perinatal health in Inner Mongolia, China, 1996-1999.

OBJECTIVE: To obtain descriptive measures of maternal and perinatal health in the Ba Men Region of Inner Mongolia, China. METHODS: Data collected from the Examination Chart for Pregnant Women for approximately 22,000 pregnancies in a three-county area of Inner Mongolia, China from December 1, 1996 through December 31, 1999 were analyzed for maternal, perinatal, and neonatal outcomes. RESULTS: Compared to selected developing countries, a higher percentage of women (99%) in this region received at least one prenatal care visit. This region was also characterized by a low percentage of low birthweight (<2.5 kg) infants (1%) and neonatal mortality rate (5 deaths per 1000 live births). CONCLUSIONS: Maternal and neonatal health outcomes in this region of Inner Mongolia were better than those in selected developing countries.

Human papillomavirus type 16 integrations in cervical tumors frequently occur in common fragile sites.

The development of cervical cancer is highly associated with human papillomavirus (HPV) infection. HPV integration into the genome of infected cervical cells is temporally associated with the acquisition of the malignant phenotype. A relationship between the sites of HPV integration in cervical cancer and the position of the common fragile sites (CFSs) has been observed at the cytogenetic level. To explore this relationship at the molecular level, we used a PCR-based method to rapidly isolate cellular sequences flanking the sites of HPV16 integrations in primary cervical tumors. Human bacterial artificial chromosome clones were isolated based on these flanking sequences and used as probes for fluorescence in situ hybridization on metaphases derived from cells cultured in the presence of aphidicolin. Our data demonstrate that HPV16 integrations in cervical tumors frequently occur within CFSs at the molecular level. In addition, we have determined the precise molecular locations of the CFSs FRA6C and FRA17B.

A Phase 2 Randomized Study Investigating the Efficacy and Safety of Myostatin Antibody LY2495655 versus Placebo in Patients Undergoing Elective Total Hip Arthroplasty.

BACKGROUND: Total hip arthroplasty relieves joint pain in patients with end stage osteoarthritis. However, postoperative muscle atrophy often results in suboptimal lower limb function. There is a need to improve functional recovery after total hip arthroplasty. OBJECTIVES: To assess safety and efficacy of LY2495655, a humanized monoclonal antibody targeting myostatin, in patients undergoing elective total hip arthroplasty. DESIGN: Phase 2, randomized, parallel, double-blind, 12-week clinical trial with a 12-week follow-up period. SETTING: Forty-two sites in 11 countries. PARTICIPANTS: Individuals (N=400) aged ≥50 years scheduled for elective total hip arthroplasty for osteoarthritis within 10 ± 6 days after randomization. INTERVENTION: Placebo or LY2495655 (35 mg, 105 mg, or 315 mg) subcutaneous injections at weeks 0 (randomization date), 4, 8, and 12 with follow up until week 24. MEASUREMENTS: Primary endpoint: probability that LY2495655 increases appendicular lean mass (operated limb excluded) by at least 2.5% more than placebo at week 12, using dual-energy x-ray absorptiometry. Exploratory endpoints: muscle strength, performance based and self-reported measures of physical function, and whole body composition over time. RESULTS: Participants: 59% women, aged 69 ± 8 years, BMI 29 ± 5 kg/m2. Groups were comparable at baseline. The primary objective was not reached as LY2495655 changes in lean mass did not meet the superiority threshold at week 12. However, LY2495655 105 and LY2495655 315 experienced progressive increases in appendicular lean mass that were statistically significant versus placebo at weeks 8 and 16. Whole body fat mass decreased in LY2495655 315 versus placebo at weeks 8 and 16. No meaningful differences were detected between groups in other exploratory endpoints. Injection site reactions occurred more often in LY2495655 patients than in placebo patients. No other safety signals were detected. CONCLUSION: Dose-dependent increases in appendicular lean body mass and decreases in fat mass were observed, although this study did not achieve the threshold of its primary objective.

Evidence for an interaction between canine synovial cell proteoglycans and link proteins.

Link proteins are glycoproteins which stabilize aggregates of proteoglycans and hyaluronic acid in cartilage. We recently identified link proteins in canine synovial cell cultures. We now find that link proteins and proteoglycans extracted from these cells under dissociative conditions sediment in the high-buoyant-density fractions of an associative cesium chloride density gradient, suggesting that link proteins interact with high-buoyant-density proteoglycans. In gradients containing [35S]sulfate-labeled synovial cell extracts, 76% of the labeled sulfate and 54% of the uronic acid is found in the high-buoyant-density fractions. Under associative conditions, Sepharose 2B elution profiles of the crude synovial cell extract, synovial cell high-buoyant-density fractions, and culture medium indicate that synovial cell proteoglycans are present in monomeric form, rather than in aggregates. Synovial cell link proteins co-elute with the [35S]sulfate-labeled material under the same conditions. These proteoglycans do not interact in vitro with exogenous hyaluronic acid. Dermatan sulfate, chondroitin sulfate and heparan sulfate are the major cell-associated sulfated glycosaminoglycans synthesized by cultured canine synovial cells, while hyaluronic acid is found in the culture medium. Although the proteoglycans synthesized by cultured synovial cells interact with link proteins, these data indicate that they do not interact with hyaluronic acid to form aggregates.

Estrogen receptor beta agonist LY500307 fails to improve symptoms in men with enlarged prostate secondary to benign prostatic hypertrophy.

BACKGROUND: To assess the efficacy and safety of LY500307, a selective estrogen receptor beta agonist, on lower urinary tract symptoms (LUTS) in patients with enlarged prostate secondary to BPH. METHODS: In a randomized, double-blind, placebo-controlled, parallel phase 2, efficacy and safety study, eligible patients with moderate to severe LUTS and prostatic enlargement (⩾30 ml) were randomized to placebo or LY500307 at 1, 3, 10 and 25 mg once daily for 24 weeks. Primary efficacy end point was change in total International Prostate Symptoms Score (IPSS) after 24 weeks. Secondary end points included changes in total prostate volume (TPV) that served as a proof of concept end point, as well as IPSS quality of life, maximum peak urine flow rate (Qmax) and PSA and safety (adverse events, laboratory test). RESULTS: A total of 414 patients were randomized when the study was terminated because of insufficient TPV reduction, based on a priori defined interim analysis. The IPSS mean change from baseline to end point was -3.4±6.8 in the placebo group and -1.3±6.6, -2.6±7.0, -3.7±6.7 and -4.4±5.7 in the 1, 3, 10 and 25 mg LY500307-treated groups, respectively (P>0.05). Similarly, no treatment effect was observed for any of the secondary efficacy measures. Incidence of adverse events was comparable between treatment groups, and no clinically meaningful changes in laboratory tests were observed. CONCLUSIONS: LY500307 was well tolerated in BPH patients with LUTS at doses up to 25 mg once daily for 24 weeks. The study was terminated early because of inadequate efficacy.

Effects of teriparatide [recombinant human parathyroid hormone (1-34)] on cortical bone in postmenopausal women with osteoporosis.

Treatment with teriparatide (rDNA origin) injection [teriparatide, recombinant human parathyroid hormone (1-34) [rhPTH(1-34)]] reduces the risk of vertebral and nonvertebral fragility fractures and increases cancellous bone mineral density in postmenopausal women with osteoporosis, but its effects on cortical bone are less well established. This cross-sectional study assessed parameters of cortical bone quality by peripheral quantitative computed tomography (pQCT) in the nondominant distal radius of 101 postmenopausal women with osteoporosis who were randomly allocated to once-daily, self-administered subcutaneous injections of placebo (n = 35) or teriparatide 20 microg (n = 38) or 40 microg (n = 28). We obtained measurements of moments of inertia, bone circumferences, bone mineral content, and bone area after a median of 18 months of treatment. The results were adjusted for age, height, and weight. Compared with placebo, patients treated with teriparatide 40 microg had significantly higher total bone mineral content, total and cortical bone areas, periosteal and endocortical circumferences, and axial and polar cross-sectional moments of inertia. Total bone mineral content, total and cortical bone areas, periosteal circumference, and polar cross-sectional moment of inertia were also significantly higher in the patients treated with teriparatide 20 microg compared with placebo. There were no differences in total bone mineral density, cortical thickness, cortical bone mineral density, or cortical bone mineral content among groups. In summary, once-daily administration of teriparatide induced beneficial changes in the structural architecture of the distal radial diaphysis consistent with increased mechanical strength without adverse effects on total bone mineral density or cortical bone mineral content.

Desipramine-induced increase in efflux of endogenous dopamine from rat hypothalamus in vitro: mechanism and specificity.

In vitro exposure of minced rat hypothalamus to desipramine (DMI) resulted in a significant elevation of the net efflux of endogenous norepinephrine (NE) and dopamine (DA) at a drug concentration as low as 10 nM. The net efflux of epinephrine was increased only by a 1000-fold greater concentration of desipramine. The increase in efflux of DA was not secondary to changes in the efflux of NE since nisoxetine elevated the efflux of NE but not of DA and the removal of calcium from the incubation medium blocked the effect of desipramine on the efflux of DA but not of NE. Elimination of calcium did not alter the "spontaneous" hypothalamic efflux of catecholamine. In contrast, desipramine did not affect the net efflux of either DA or NE from the olfactory tubercle or striatum at concentrations of less than 100 microM. At this concentration, the efflux of DA was significantly increased only in the striatum, while the efflux of NE was reduced in the striatum but increased in the olfactory tubercle. Again, in contrast to the hypothalmus, the removal of calcium from the medium markedly reduced "spontaneous" efflux of catecholamine and the desipramine induced efflux of NE, but not the increase in striatal DA efflux produced by desipramine. The results indicate that marked regional differences exist in brain in the ability of desipramine or calcium removal to alter the efflux of both endogenous DA and NE, and suggest that hypothalamic DA and NE neurons are uniquely sensitive to the effects of desipramine.

Synovial fluid markers in osteoarthritis.

Exploration of the mechanisms responsible for breakdown and repair of articular cartilage in osteoarthritis has promoted interest in the potential use of cartilage-derived molecules as markers of cartilage metabolism in this disease. Many of the macromolecules detectable in synovial fluid have been evaluated as possible surrogate markers of the severity or activity of disease processes. Measurements of the synovial fluid concentration of any marker without due consideration of the fate of the molecule in the joint cavity are likely to be misleading and insufficient to cement a relationship between marker concentration and the severity of articular pathology.

Neurogenic acceleration of osteoarthrosis. The effects of previous neurectomy of the articular nerves on the development of osteoarthrosis after transection of the anterior cruciate ligament in dogs.

The development of osteoarthrosis in unstable knee joints of dogs after transection of the anterior cruciate ligament is greatly accelerated when the afferent nerve fibers from the ipsilateral hindlimb have been interrupted by dorsal root ganglionectomy before transection. The purpose of the current study was to determine whether partial loss of the afferent fibers from the knee joints of dogs, accomplished by neurectomy of the primary articular nerves before transection of the ligament, also accelerates the development of osteoarthrosis. Osteoarthrosis did not develop in dogs that had had transection of the medial, posterior, and lateral articular nerves to the left knee joint but had an intact anterior cruciate ligament. Osteoarthrosis developed in all dogs that had had transection of the anterior cruciate ligament. However, the osteoarthrotic lesions, as gauged by histological and macroscopic criteria, were more frequent and severe in dogs that had had neurectomy before transection than in those that had intact sensory nerves and an unstable joint (p less than or equal to 0.05). A subchondral fracture occurred in three dogs that had had neurectomy and had an unstable joint but in none of the dogs that had intact sensory nerves and an unstable joint.

A cross-sectional study of triallate exposure and neurological health among workers at a pesticide manufacturing and formulating facility.

AIMS: To evaluate the relation between an indicator of cumulative exposure to triallate and selected measures of neurological function, including nerve conduction, the prevalence of certain neurological deficits as determined by a medical examination, and vibration perception threshold testing in workers at a pesticide manufacturing plant. METHODS: Subjects were 50 workers with high estimated triallate exposure ("high triallate" group) and 50 workers with no or low triallate exposure ("no/low triallate" group). Industrial hygienists used existing work histories and personal knowledge of plant operations to develop a triallate score. In-person interviews elicited information on past medical history and on occupational and non-occupational exposures. A neurologist carried out nerve conduction tests of the sural and the peroneal nerves, a standardised neurological examination, and vibration sensation testing. RESULTS: Differences between the high and the no/low triallate groups were minimal for all but one of the six nerve conduction tests, for the prevalence of neurological abnormalities, and for vibration sensation perception. The high triallate group had lower mean sural nerve peak amplitude than the no/low triallate group (11.7 v 15.2 microV, p = 0.03). This difference was reduced when adjusted for other potential risk factors (12.5 v 14.5 microV, p = 0.25) and was not associated with cumulative triallate score. We also noted several associations between factors other than triallate and nerve conduction measures. CONCLUSION: The results were consistent with the absence of an association between triallate and measures of neurological function.

Racial differences in home ownership and home equity among preretirement-aged households.

This article measures the racial disparities in home ownership and home equity among preretirement-aged households. It computes the proportion of the racial gap explained by discrimination in housing and credit markets. Maximum likelihood and nonlinear least squares estimates are obtained for models of home ownership probabilities and home equity, conditional on home ownership, yielding computations for expected home equity for black and white households. The results reveal an average discriminatory gap in expected home equity as a percent of the actual gap of 55%. In the top third of the family income distribution, the measured discriminatory gap is 82%; in the middle third it is 83%; in the lowest third it is 62%.

Lesions and distribution of viral antigen following an experimental infection of young seronegative calves with virulent bovine virus diarrhea virus-type II.

During the past several years, acute infections with bovine viral diarrhea virus (BVDV) have been causally linked to hemorrhagic and acute mucosal disease-like syndromes with high mortality. The majority of BVDVs isolated in such cases have been classified as type II on the basis of genetic and antigenic characteristics. It was our objective to examine clinical disease, lesions and potential sites of viral replication, following experimental BVDV type II infection in young calves. On approximately day 35 after birth, calves that had received BVDV-antibody-negative colostrum were infected by intranasal inoculation of 5 x 10(5) TCID50 of BVDV type II isolate 24,515 in 5 mL of tissue culture fluid (2.5 mL/nostril). Calves were monitored twice daily for signs of clinical disease. Approximately 48-72 h after infection, all calves developed transient pyrexia (39.4-40.5 degrees C) and leukopenia. Beginning on approximately day 7 after infection, all calves developed watery diarrhea, pyrexia (40.5-41.6 degrees C), marked leukopenia (> or = 75% drop from preinoculation values), variable thrombocytopenia, and moderate to severe depression. Calves were euthanized on days 10, 11, or 12 after infection due to severe disease. Gross and histological lesions consisted of multifocal bronchointerstitial pneumonia (involving 10%-25% of affected lungs), bone marrow hypoplasia and necrosis, and minimal erosive lesions in the alimentary tract. Immunohistochemical staining for BVDV revealed widespread viral antigen usually within epithelial cells, smooth muscle cells and mononuclear phagocytes in multiple organs, including lung, Peyer's patches, gastric mucosa, thymus, adrenal gland, spleen, lymph nodes, bone marrow, and skin. This BVDV type II isolate caused rapidly progressive, severe multisystemic disease in seronegative calves that was associated with widespread distribution of viral antigen and few gross or histological inflammatory lesions.

The effects of sample selection bias on racial differences in child abuse reporting.

OBJECTIVE: The aim was to examine whether design features of Wave 1, 1980 National Incidence Study (NIS) data resulted in sample selection bias when certain victims of maltreatment were excluded. METHOD: Logistic regression models for the probability of child abuse reports to the child protective services (CPS) were estimated using maximum likelihood methods for Black (n = 511) and White (n = 2499) child abuse cases. The models were estimated with and without correction for selection bias using a two-step procedure proposed by Heckman. RESULTS: Substantial differences were found in the characteristics of Black and White victims by source of report and by type of maltreatment. Also found were sizeable differences within each racial group between sampled agencies and nonsampled agencies. Sample selection bias affected the estimation of both White and Black child abuse reporting rates. In the Black sample, however, the effect of sample selection bias was to reduce the statistical significance of the impacts of reporting agency and physical and sexual abuse on report rates. In the White sample, most significant factors in the basic model remained statistically significant with correction for selection bias. CONCLUSIONS: Selection bias was found to be caused by the exclusion of family, friends, and neighbors in the NIS sample design. Such exclusion has the effect of altering the interpretation of the determinants of child abuse reporting among Blacks, but not among Whites. Thus, conclusions about racial differences in child maltreatment must be reached cautiously, given the NIS study design.

Effects of extreme heat on teeth with implications for histologic processing.

This pilot study examined teeth subjected to extreme heat under laboratory conditions, and the subsequent effect of decalcification and histologic processing. Physical and microscopic findings were evaluated in relation to temperature and duration of thermal insult. Microscopic examination following decalcification and histologic processing revealed changes including severe tissue fragmentation, vapor bubbles within dentinal tubules, altered histologic staining, charring and tissue shrinkage. Dentin appeared to be the most reliable microscopic identifier of incinerated dental tissues. Temperatures above 600 degrees C strongly predicted tooth disintegration following decalcification. This finding has implications in incineration cases where histologic evidence must be maintained and examined intact.

Skeletal dosimetry via NMR microscopy: investigations of sample reproducibility and signal source.

Nuclear magnetic resonance microscopy has been used for several years as a means of quantifying the 3D microarchitecture of the cancellous regions of the skeleton. These studies were originally undertaken for the purpose of developing non-invasive techniques for the early detection of osteoporosis and other bone structural changes. Recently, nuclear magnetic resonance microscopy has also been used to acquire this same 3D data for the purpose of both (1) generating chord length data across bone trabeculae and marrow cavities and (2) generating 3D images for direct coupling to Monte Carlo radiation transport codes. In both cases, one is interested in the reproducibility of the dosimetric data obtained from nuclear magnetic resonance microscopy. In the first of two studies, a trabecular bone sample from the femoral head of a 51-y-old male cadaver was subjected to repeated image acquisition, image processing, image coupling, and radiation transport simulations. The resulting absorbed fractions at high electron energies (4 MeV) were shown to vary less than 4% among four different imaging sessions of the same sample. In a separate study, two femoral head samples were imaged under differing conditions of the NMR signal source. In the first case, the samples were imaged with intact marrow. These samples were then subjected to marrow digestion and immersed in Gd-doped water, which then filled the marrow cavities. Energy-dependent absorbed fraction profiles for both the marrow-intact and marrow-free samples showed essentially equivalent results. These studies thus provide encouragement that skeletal dosimetry models of improved patient specificity can be achieved via NMR microscopy in vivo.

Dental erosion: diagnostic-based noninvasive treatment.

Lesions that result from dental erosion can be difficult to recognize--particularly when abrasion and attrition are also present. Consequently, dental erosion is often misdiagnosed and mistreated by radical restorative modalities that compromise the vitality of the pulp. This article provides clinicians with knowledge concerning the diagnosis of the complex lesions of dental wear and demonstrates the conservative treatment of this condition. Two cases that exhibit marked tooth wear in anterior teeth and their subsequent restoration utilizing occlusal principles and composite resin are presented.

Maternal drinking water arsenic exposure and perinatal outcomes in inner Mongolia, China.

BACKGROUND: Bayingnormen is a region located in western Inner Mongolia China, with a population that is exposed to a wide range of drinking water arsenic concentrations. The relationship between maternal drinking water arsenic exposure and perinatal endpoints (term birth weight, preterm birth, stillbirth and neonatal death) in this region was evaluated in this study. METHODS: An analysis was conducted of all singleton deliveries in a defined geographical area of Inner Mongolia from December 1996 to December 1999 (n=9890). Outcome and covariate data were abstracted from prenatal care records. Exposure was based on well-water measures for the maternal subvillage. Mean birth weight at term was compared across four arsenic categories using analysis of covariance. ORs for stillbirth, preterm birth and neonatal death were estimated by logistic regression with arsenic exposure dichotomised at 50 microg/l. RESULTS: Term birth weight was 0.05 kg higher (95% CI 0.02 to 0.08) in the highest exposure category (>100 microg/l) compared to the reference (below limit of detection to 20 microg/l). Arsenic >50 microg/l was associated with an increased risk of neonatal death (OR 2.01, 95% CI 1.12 to 3.59). No relationship was found between maternal arsenic exposure and preterm or stillbirth delivery. CONCLUSIONS: At the levels observed in our study, arsenic does not appear to contribute to adverse birth outcomes. Exposure may play a role in neonatal death; however, the neonatal death rate in this population was low and this potential association merits further research.