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.

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.

One-year change in radiographic joint space width in patients with unilateral joint space narrowing: data from the Osteoarthritis Initiative.

OBJECTIVE: To examine the rate of joint space width (JSW) loss in both knees of patients with unilateral medial joint space narrowing (JSN) at baseline. METHODS: Cases were selected from a pool of 2,678 subjects enrolled in the Osteoarthritis Initiative cohort. Inclusion criteria for the present study were unilateral medial JSN, bilateral frequent knee pain, and body mass index (BMI) > or = 25 kg/m(2). Baseline and 1-year fixed flexion radiographs of both knees were read (blinded to time point) using an automated algorithm for minimum JSW and JSW at 4 fixed locations in the medial compartment. RESULTS: Sixty-seven participants met the inclusion criteria: 43 women and 24 men, with mean +/- SD age 60 +/- 9 years and mean +/- SD BMI 31 +/- 4 kg/m(2). Thirty-seven subjects (55%) had > or = 1 definite tibiofemoral osteophyte. The average progression in no-JSN knees was comparable with that in JSN knees (approximately -0.2 mm/year). However, JSW change was more variable in no-JSN knees, resulting in standardized response means (SRMs; the mean/SD) of approximately -0.24 in no-JSN knees versus approximately -0.41 in JSN knees on average at the 4 fixed locations, and SRMs of -0.24 and -0.35, respectively, for minimum JSW. Young age and high BMI were associated with increased progression, especially in JSN knees. CONCLUSION: JSN and no-JSN knees progressed at a comparable rate, but a wider distribution of JSW change in no-JSN knees resulted in a poorer sensitivity to change in these knees.

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.

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.

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.

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.

Following treatment of myogenous TMD patients with the temporomandibular opening index: an initial report.

Limitation of mandibular movement is one of the cardinal signs of temporomandibular disorders (TMD), usually assessed by measurement of maximum voluntary mouth opening. A new measure of assessing mandibular mobility, the temporomandibular opening index (TOI), is less dependent on variables such as age, gender and ramus length. It has also been found to be useful to categorize patients. This study examined changes in TOI as treatment progressed in a group of myogenous TMD patients. Seven patients with myogenous TMD were included in the study and the TOI determined at 0 and 2 weeks, 1 and 6 months after initiation of treatment. Treatment outcome was assessed on a 4 point scale, 0=none, 1=mild, 2=moderate, and 3=severe. Headache, neckache, pain (joints and muscles) and joint sounds were assessed. Nine patients with no signs or symptoms of TMD were included to obtain a normal TOI. The mean TOI of the patient group was 16.4% (s.d.=11.2%) initially and 3.95% (s.d.=1.0%) at 6 months, while mean treatment scores changed from 12.57 (s.d.=3.05) to 1.43 (s.d.=1.90). The mean TOI of the control group was 3.63 (s.d.=0.74). A paired t-test showed that the TOI decreased significantly with time (P=0.02) while there was a concomitant decrease in treatment score (P=0.0003) over the same period. The TOI may be a useful method of following treatment of this group of myogenous TMD patients.

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.

Severity of medial meniscus damage in the canine knee after anterior cruciate ligament transection.

OBJECTIVE: To examine the relationship between the severity of cartilage damage and the severity of meniscus damage after transection of the anterior cruciate ligament (ACLT) in adult dogs. DESIGN: Data were obtained from 40 dogs which underwent ACLT and from three additional sham-operated dogs that were subjected to arthrotomy but not ligament transection. Joint pathology was analysed 12, 24 or 32 weeks after surgery. The severity of damage to the articular cartilage on the femoral condyle and tibial plateau was graded with a scoring system based on that of the Sociètè Française d'Arthroscopie and meniscus damage was graded on a 0-4 scale. RESULTS: No damage to the meniscus or articular cartilage was observed 12 weeks after surgery in the dogs subjected only to arthrotomy. In contrast, tears of the medial meniscus were observed in two of 10 (20%) dogs examined 12 weeks after ACLT. The incidence of severe tears increased to 86% and 84% after 24 weeks and 32 weeks, respectively. Damage to the lateral meniscus was mild, with only 7.5% of all dogs with a cruciate-deficient knee having a bucket handle or complete tear. Most of the unstable knees exhibited ulceration of the articular cartilage of the femoral condyles and tibial plateaus 12 weeks (mean chondropathy score+/-standard deviation 11.9+/-8.5, N=10), 24 weeks (7.9+/-5.0, N=7), and 32 weeks (7.1+/-5.5, N=23) after ACLT. The mean chondropathy scores for the tibial plateaus were similar to those for the femoral condyles. No correlation was apparent between the severity of cartilage damage and of meniscus damage for either joint surface. CONCLUSION: Damage to the medial meniscus is a consistent feature of the pathology which develops in the canine knee after ACLT, but the severity of cartilage damage is not correlated with the severity of meniscal damage.

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.

Effect of intraarticular hyaluronan injection on synovial fluid hyaluronan in the early stage of canine post-traumatic osteoarthritis.

OBJECTIVE: To determine how the quantity and molecular weight of synovial fluid hyaluronan (HA) within the synovial fluid (SF) of osteoarthritis (OA) joints is affected by intraarticular injection of HA. METHODS: Dogs in which OA was induced by transection of the anterior cruciate ligament received 5 weekly injections of HA (1.5 x 10(6) Da) in saline (10 mg/0.67 ml) or an equal volume of saline into the operated knee, beginning the day after surgery. Immediately before each injection, SF was aspirated and the volume of SF and the concentration of HA was measured (uronic acid), and the molecular weight of the HA in each sample was estimated by electrophoresis in agarose. RESULTS: The volume of SF in the unstable knee increased after surgery, and the molecular weight decreased from approximately 2.5 x 10(6) Da to approximately 2 x 10(6) Da. Injection of HA did not affect the volume of SF or average molecular weight of HA in samples obtained immediately before each injection or at the end of the experiment, 12 weeks after surgery. The SF HA concentration fell from a baseline value of 2.3 +/- 0.1 mg/ml to 1.1 +/- 0.2 mg/ml the day after surgery and remained low throughout the course of injections. The HA concentration 12 weeks after surgery in the HA injected knees was approximately 40% lower than the preoperative value, although it increased slightly relative to saline injected knees (1.4 +/- 0.3 vs 1.1 +/- 0.01 mg/ml, respectively; p = 0.04). CONCLUSION: Intraarticular injection of HA did not alter the volume of SF or molecular weight of HA in SF of OA canine knees, nor did it restore the HA concentration to that of normal canine SF.

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.

The temporomandibular opening index (TOI) in patients with closed lock and a control group with no temporomandibular disorders (TMD): an initial study.

Mandibular movement may be assessed by measuring maximum mouth opening. This is a linear measurement from the maxillary to the mandibular incisal edge and is affected by gender, age and ramus length. It cannot be used to classify patients. The temporomandibular opening index (TOI) appears to be independent of these variables and has been shown to differ for different categories of patients with temporomandibular disorders (TMD). This study examined the TOI in a group of 11 patients with closed lock and a control group of 11 individuals with no signs or symptoms of TMD. The group with closed lock had a significantly different TOI from that of the control group (P < 0.001) according to the Mann-Whitney U-test. This suggests that the TOI may have greater diagnostic value than linear mouth opening.

Myogenous temporomandibular disorder patients and the temporomandibular opening index.

Limited mandibular movement is one of the cardinal signs of temporomandibular disorders, and is usually assessed by measurement of mouth opening. Linear measurement of mouth opening does not discriminate between diagnostic groups and has been shown to be influenced by gender, age and ramus length. A new temporomandibular opening index, however, can differentiate between diagnostic groups and is not influenced by the above variables. When patients with a myogenous temporomandibular disorder were examined, the temporomandibular opening index distinguished two subgroups, the first with values about the lower quartile and the second with values about the upper quartile. A similar identification of two subgroups was seen in electromyographic studies of myogenous temporomandibular disorder patients.

Synovial fluid glycosaminoglycan concentration does not correlate with severity of chondropathy or predict progression of osteoarthritis in a canine cruciate deficiency model.

OBJECTIVE: Considerable interest exists today in biochemical or immunochemical tests for monitoring the progression of osteoarthritis (OA). It has been suggested that measurements made on synovial fluid (SF) will more accurately reflect the magnitude of cartilage destruction in an index joint than those performed on serum. However, we have shown that the synovitis that occurs in OA affects the rate of protein clearance from the joint. We tested the hypothesis that if adjusted for clearance rate, the SF concentration of cartilage proteoglycans (PG) estimates severity of chondropathy and predicts progression of cartilage damage more accurately than if clearance is not taken into account. METHODS: Clearance of radioiodinated serum albumin (RISA), a surrogate for the clearance of PG, was measured in 19 adult dogs at baseline and again 16 weeks and 32 weeks after anterior cruciate ligament transection (ACLT). Severity of chondropathy was determined arthroscopically after 16 weeks of instability and at postmortem 32 weeks after ACLT. RESULTS: Adjustment for the RISA clearance rate showed that the SF PG concentration markedly underestimated the quantity of PG released from the OA cartilage. Regardless of whether the concentration was adjusted for clearance, no correlation existed between the SF PG level and the severity of chondropathy. Further, the SF concentration of PG 16 weeks after ACLT failed to predict severity of cartilage damage at postmortem. CONCLUSION: SF concentration of a cartilage derived molecule is unlikely to predict the course of cartilage damage in an OA joint over time or in response to treatment with a potential disease modifying OA drug.

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.

Effects of a bisphosphonate on bone histomorphometry and dynamics in the canine cruciate deficiency model of osteoarthritis.

OBJECTIVE: To examine the effect of the bisphosphonate NE- 10035 on bone histomorphometry and bone dynamics in dogs after transection of the anterior cruciate ligament (ACL), and to determine, in a placebo controlled trial, whether treatment modified the severity of pathologic changes of osteoarthritis (OA) in the unstable joint. METHODS: Ten adult male mongrel dogs underwent ipsilateral ACL transection. Five dogs then received daily subcutaneous injections of NE-10035 on 5 days per week for 12 weeks beginning the day after surgery. The other 5 dogs served as concurrent OA controls and received subcutaneous injections of saline on the same schedule. At sacrifice, 12 weeks after ACL transection, the articular cartilage and synovium of both knees of each dog were evaluated grossly and histologically and the water content and uronic acid concentration of the articular cartilage was determined. Fifteen days before sacrifice, each dog was injected with the fluorochrome label calcein. The injection regimen was repeated 10 days after the initial date. At sacrifice, static and dynamic variables of bone formation were assessed and bone resorption was quantified. RESULTS: In the OA knee of the control group, bone formation and resorption were markedly increased. NE-10035 markedly reduced both formation and resorption of cancellous subchondral bone, but had no effect on osteophyte formation or pathologic changes of OA in the articular cartilage, which were mild in both treatment groups. Water content of the OA cartilage was increased by about 8% in both treatment groups. However, among the controls, the mean uronic acid concentration of the OA cartilage was increased by about 30% in comparison with values for the contralateral knee, while in the NE-10035 treatment group the mean uronic acid concentration of OA knee cartilage was about 15% lower in the active treatment group than in cartilage from the contralateral knee (p = 0.003 for the difference in OA knee uronic acid concentration between the 2 treatment groups, relative to that in the contralateral knee). CONCLUSION: The antiresorptive agent employed in this study effectively reduced turnover of subchondral bone in the OA joint, consistent with the coupling of bone formation to bone resorption at that site. Nonetheless, over the 12 week period of the study it had no effect on osteophyte formation, in which bone formation occurs via enchondral ossification and is not linked to bone resorption, and, despite the clear inhibition of bone turnover in the OA knee of the active treatment group, did not affect the severity of cartilage changes of OA. It should be noted, however, that although treatment with this antiresorptive agent did not affect the level of chondropathy, the cartilage changes in both treatment groups were relatively mild and the sample size relatively small. Additional studies with a larger number of animals and a longer period of observation (to increase the severity of pathology) are warranted to determine whether the inhibition of bone turnover and the decrease in proteoglycan concentration that resulted from therapy will affect articular cartilage degeneration in the OA joint.

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.