Differential effects of teriparatide on regional bone formation using 18F‐fluoride positron emission tomography

Teriparatide increases skeletal mass, bone turnover markers, and bone strength, but local effects on bone tissue may vary between skeletal sites. We used positron emission tomography (PET) to study ¹⁸F‐fluoride plasma clearance (K_i) at the spine and standardized uptake values (SUVs) at the spine, pelvis, total hip, and femoral shaft in 18 postmenopausal women with osteoporosis. Subjects underwent a 1‐hour dynamic scan of the lumbar spine and a 10‐minute static scan of the pelvis and femurs at baseline and after 6 months of treatment with 20 µg/day teriparatide. Blood samples were taken to derive the arterial input function and lumbar spine K_i values evaluated using a three‐compartment model. SUVs were calculated for the spine, pelvis, total hip, and femoral shaft. After 6 months treatment with teriparatide, spine K_i values increased by 24% (p = .0003), while other model parameters were unchanged except for the fraction of tracer going to bone mineral (k₃/[k₂ + k₃]), which increased by 23% (p = .0006). In contrast to K_i, spine SUVs increased by only 3% (p = .84). The discrepancy between changes in K_i and SUVs was explained by a 20% decrease in ¹⁸F^? plasma concentration. SUVs increased by 37% at the femoral shaft (p = .0019), 20% at the total hip (p = .032), and 11% at the pelvis (p = .070). Changes in bone turnover markers and BMD were consistent with previous trials. We conclude that the changes in bone formation rate during teriparatide treatment as measured by ¹⁸F^? PET differ at different skeletal sites, with larger increases in cortical bone than at trabecular sites. © 2011 American Society for Bone and Mineral Research.     

The Mitochondrial Genome And Human Mitochondrial Diseases

To date, more than 100 point mutations and several hundreds of structural rearrangements of mitochondrial DNA (mtDNA) are known too be connected with characteristic neuromuscular and other mitochondrial syndromes varying from those causing death at the neonatal stage to diseases with late ages of onset. The immediate cause of mitochondrial disorders is a defective oxidative phosphorylation. Wide phenotypic variation and the heteroplasmy phenomenon, which some authors include in mutation load, are characteristic of human mitochondrial diseases. As the numbers of cases identified and pedigrees described increase, data on the genotype-phenotype interaction and the structure and frequency of pathogenic and conditionally pathogenic mtDNA mutations in human populations are rapidly accumulated. The data on the genetics and epidemiology of mitochondrial diseases are not only important for differential diagnosis and genetic counseling. Since both neutral and mildly pathogenic mutations of mtDNA are progressively accumulated in maternal phyletic lines, molecular analysis of these mutations permits not only reconstruction of the genealogical tree of modern humans, but also estimation of the role that these mutations play in natural selection.     

Use of monoclonal antibodies for the histopathological diagnosis of human malignancy

This paper describes the use of a panel of seven monoclonal antibodies (selected so as to include reagents reactive with both epithelial and lymphoid cells) for distinguishing between anaplastic carcinoma and high grade lymphoma. Details are given of the immunohistological reactions of these antibodies against a wide range of both normal and malignant tissues and of a number of practical instances in which use of the antibody panel enabled a diagnosis to be made when routine histological examination had been inconclusive.     

Anin vitro model for studying mechanisms underlying synoviocyte-mediated cartilage invasion in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease of joints involving the pathological development of an invasive and destructive pannus tissue which contributes to the loss of cartilage and bone. To further analyze the process of cartilage degradation and invasion, we have developed an in vitro model composed of cartilage matrix and synoviocytes (isolated from RA pannus tissue, as well as normal synovial membrane). The matrix is derived from pig articular cartilage and contains collagen type II and proteoglycans and is similar in composition to human cartilage. Data generated from this model reveal that synoviocytes isolated from RA pannus tissue invaded cartilage matrix in a manner which directly correlated with the severity of the disease. Analysis of mechanisms associated with the invasive process demonstrate that highly invasive RA synoviocytes maintain a round morphology during attachment and spreading on cartilage matrix, compared with their normal counterparts. Furthermore, the level of secretion of matrix metalloproteinase (MMP) activity was shown to correlate with the RA phenotype, which could be modulated with a novel MMP inhibitor. Normal synoviocytes could be "converted" to an RA phenotype by specific inflammatory cytokines, such that invasion of cartilage matrix was augmented by culturing these cells in the presence of 5 U/ml IL-1b or 18 U/ml TGFb. Invasion was inhibited by 150 U/ml TNFa, and unaffected by 100 ng/ml PDGF. In addition, synovial fluid from RA patients induced invasion of normal synoviocytes, in a concentration dependent manner, from 150% to 460%; however, synovial fluid from another inflammatory arthritidy (Crohn's) did not augment invasion to the same degree. Moreover, this "conversion effect" appears to be specific for synoviocytes, since similar effects could not be achieved with human skin fibroblasts. This in vitro model of synoviocyte-mediated cartilage invasion allows for further molecular characterization of the invasive properties of the synoviocyte which contribute to RA.     

An Evaluation of the Changes in Malocclusion Index Scores Over a 25-year Period

BACKGROUND: The measured values of specific traits of occlusion may be subject to significant change due to growth and maturation of the dentofacial structures. Some traits may show improvement while others may show deterioration. Rarely is there an opportunity to examine a sample of occlusions 25 years after the acquisition of the original set of records. This study examines the changes in traits of occlusion in a sample of 46 subjects who were originally examined between 1971-1973 and for whom records were again obtained in 1998. METHODS: The 46 patients were a sub-group of a previously selected randomised school-based sample and study models obtained in 1971-1973 were still available. New models for each patient were obtained in 1998. Of the 46 subjects, only eight had received orthodontic treatment. RESULTS: Assessments of the changes in specific traits were made using the methods proposed in the Harry L Draker, California Modification (HLD Cal Mod) index. This simple index was chosen because the main component traits were well defined and, when analysed separately, reflected changes with time. The total index score gave a broad indication of the global changes in the individual's occlusion. The five basic traits of the HLD index include overjet, overbite, openbite, mandibular protrusion and labio-lingual spread. Three additional traits (ectopic eruption, anterior crowding and posterior crossbite) are used in the HLD Cal Mod index. These traits provided a useful reflection of occlusal changes with time. Measurements were made with reference to specifications and the details outlined in the HLD Cal Mod protocol. The results revealed an increase in total index scores over time with a significant increase in lower labio-lingual spread associated with an increased score in anterior crowding. Overjet and overbite, however, displayed a significant decrease with time. CONCLUSIONS: These findings are in keeping with previous studies and highlight the importance of time as a significant issue in the assessment of occlusion.     

Stray dog trade fuelled by dog meat consumption as a risk factor for rabies infection in Calabar,southern Nigeria

Background

Rabies is a preventable zoonosis with the highest case fatality of any disease in the world. In the developing world, it is transmitted mainly by dog bites. In parts of southern Nigeria, dog meat is a delicacy.

Objective

To highlight trade in stray dogs as a major risk factor for rabies in animals and humans in south-south Nigeria.

Method

Patients admitted into the University of Calabar Teaching Hospital (UCTH) with a diagnosis of rabies between July and October 2012 were analysed for risk factors, post exposure prophylaxis (PEP), health seeking behaviour and outcome. Focused group interview were also conducted among traders/handlers of stray dogs.

Results

Ten cases of rabies in subjects aged 3 to 52 years were recorded in these five months period. Eight of the cases were male and apparently got infected directly or indirectly through the trade in stray dogs for human consumption. None had proper PEP and all patients died.

Conclusion

Stray dog trade, fuelled by eating of dog meat, is a risk factor for human and animal rabies in Calabar, southern Nigeria. Culling of stray dogs, control of stray dogs'' trade and public enlightenment on PEP is recommended.     

Estrogen-induced microsatellite DNA alterations are associated with Syrian hamster kidney tumorigenesis

Exposure to estrogens is associated with an increase in cancers, including malignancies of the breast and uterus in humans, and of the kidney in hamsters. DNA damage induced by metabolic activation of estrogen has been postulated to result in gene mutations critical for the development of estrogen-induced kidney tumors in hamsters. As part of our examination of the genetic consequences of estrogen-induced DNA damage, we searched for estrogen-induced alterations in microsatellite DNA, a frequent site of mutation in tumors. Genomic DNA isolated from kidney of hamsters treated with estradiol, from estrogen-induced kidney tumors and from untreated age-matched controls, was examined by Southern blot analysis with three multi-locus oligonucleotide probes: (GACA)4, (CAC)6 and (CAG)6. Alterations in DNA fragments containing GACA and CAC tandem repeats were detected in kidney DNA of hamsters treated with hormone for 3 and 4 months, whereas no such effects were seen in control animals. In estrogen-induced tumors, microsatellite alterations were observed in fragments that contain these same two repeat sequences and also CAG repeat sequences. The induction of microsatellite alterations by estradiol in kidney DNA preceding estrogen-induced renal malignancy may play a role in hormone-induced tumorigenesis.      

Neutrophil interaction with influenza-infected epithelial cells

An in vitro model system was used to study the early neutrophil response to influenza-infected epithelia. In the absence of serum, neutrophil adherence to influenza-infected confluent monolayers of Madin-Darby canine kidney epithelial cells (MDCK) was approximately 590 times greater than neutrophil binding to control cultures. The leukocytes bound specifically to virus-infected cells. Neutrophil adherence to influenza-infected MDCK cells was monitored during the course of one replication cycle, and binding began at a time (4.5 hours) that coincided with viral protein insertion in the apical cell membrane. Ultrastructural examination at 4.5 hours showed that greater than 90% of the neutrophils adhered to the epithelial cell membrane in the absence of budding virus and, at 6.5 hours, 100% of the neutrophils adhered to the epithelium with emerging virions. The number of neutrophils bound to influenza-infected MDCK cells was not affected by the presence or absence of calcium or magnesium but did depend on the amount of viral inoculum and on the temperature of the culture. In direct contrast to hemadsorption of RBCs, neutrophil binding to influenza-infected MDCK cells was 100% greater at 37 degrees C than at 4 degrees C. The neutrophil surface molecules that bound influenza virus appeared to become functionally polarized because the adherence of neutrophils to budding influenza virus or to a virus-coated surface inhibited the neutrophils from binding additional influenza virus to their nonadherent surface.     

Gleason score and tumor laterality in radical prostatectomy and transrectal ultrasound-guided biopsy of the prostate: a comparative study

We aimed to compare Gleason score and tumor laterality between transrectal ultrasound-guided biopsy of the prostate (TRUSBX) and radical prostatectomy (RP). Some factors that could cause a discrepancy in results between these two procedures were also evaluated. Among the 318 cases reviewed, 191 cases were selected for inclusion in this comparative study. We divided the patients into two groups using the Gleason score: an intermediate/high-grade group (≥7) and a low-grade group (<6). Exploratory analyses were conducted for comparisons between groups. We also performed comparisons between TRUSBX and RP for tumor laterality. TRUSBX overestimated 6% and underestimated 24% cases in comparison with RP for Gleason score, and overestimated 2.6% and underestimated 46% cases compared with RP for tumor laterality. Biopsy specimens were slightly smaller in TRUSBX cases with underestimated tumor laterality (P < 0.05), and no relationship between the biopsy specimen size and underestimated Gleason score in TRUSBX was found. Prostatic volume showed no statistical correlation with the likelihood of under or overestimation (P > 0.05). Thus, our study showed that TRUSBX has a high likelihood of underestimating both the Gleason score and tumor laterality in prostate cancer (PCa). The size of the fragment appears to be an important factor influencing the likelihood of laterality underestimation and Gleason score overestimation via TRUSBX. Due to the high likelihood of underestimation of the Gleason score and tumor laterality by 12-core prostate biopsy, we conclude that this type of biopsy should not be used alone to guide therapy in PCa.