Risedronate in adults with osteogenesis imperfecta type I: increased bone mineral density and decreased bone turnover, but high fracture rate persists.

UNLABELLED: Bisphosphonates can increase bone mineral density (BMD) in children with osteogenesis imperfecta (OI). In this study of adults with OI type I, risedronate increased BMD at lumbar spine (but not total hip) and decreased bone turnover. However, the fracture rate in these patients remained high. INTRODUCTION: Intravenous bisphosphonates given to children with OI can increase BMD and reduce fracture incidence. Oral and/or intravenous bisphosphonates may have similar effects in adults with OI. We completed an observational study of the effect of risedronate in adults with OI type I. METHODS: Thirty-two adults (mean age, 39 years) with OI type I were treated with risedronate (total dose, 35 mg weekly) for 24 months. Primary outcome measures were BMD changes at lumbar spine (LS) and total hip (TH). Secondary outcome measures were fracture incidence, bone pain, and change in bone turnover markers (serum procollagen type I aminopropeptide (P1NP) and bone ALP). A meta-analysis of published studies of oral bisphosphonates in adults and children with OI was performed. RESULTS: Twenty-seven participants (ten males and seventeen females) completed the study. BMD increased at LS by 3.9% (0.815 vs. 0.846 g/cm(2), p = 0.007; mean Z-score, -1.93 vs. -1.58, p = 0.002), with no significant change at TH. P1NP fell by 37% (p = 0.00041), with no significant change in bone ALP (p = 0.15). Bone pain did not change significantly (p = 0.6). Fracture incidence remained high, with 25 clinical fractures and 10 major fractures in fourteen participants (0.18 major fractures per person per year), with historical data of 0.12 fractures per person per year. The meta-analysis did not demonstrate a significant difference in fracture incidence in patients with OI treated with oral bisphosphonates. CONCLUSIONS: Risedronate in adults with OI type I results in modest but significant increases in BMD at LS, and decreased bone turnover. However, this may be insufficient to make a clinically significant difference to fracture incidence.

Inhibitory effect of quercetin on periodontal pathogens in vitro.

Actinobacillus actinomycetemcomitans (Aa) and Porphyromonas gingivalis (Pg) are bacteria strongly associated with early onset, progressive and refractory periodontal disease and associated alveolar bone loss. Quercetin is a flavonoid found in many foods including apples, onions and tea. The aim of this study was to evaluate the effect of quercetin on in vitro growth of periodontal pathogens Aa and Pg. For comparison, quercetin's effect on several oral microbes was also evaluated. Different concentrations of quercetin solution were added to calibrated suspensions of Aa and Pg. All suspensions were incubated for 1, 3, 6, and 24 h in an anaerobic chamber at 37 degrees C. At each time point, selected dilutions from each culture broth were plated on blood agar plates. Colonies appearing on blood agar plates were visually counted on 3 days for Aa and 5 days for Pg. Minimum inhibitory concentrations of both periodontal pathogens were also determined. Both periodontal bacteria showed a significant decrease (p < 0.05) in viable counts after 1 h. No colony forming units of Pg could be observed after 24 h. The results suggest that quercetin possesses significant antimicrobial properties on periodontal pathogens in vitro.

Vax1 Plays an Indirect Role in the Etiology of Murine Cleft Palate.

Cleft lip with or without palate (CLP) and isolated cleft palate (CP) are common human developmental malformations with a complex etiology that reflects a failure of normal facial development. VAX1 encodes a homeobox-containing transcription factor identified as a candidate gene for CLP in human populations, with targeted deletion in mice associated with multiple anomalies, including disruption of the visual apparatus and basal forebrain, lobar holoprosencephaly, and CP. We have investigated Vax1 function during murine palatogenesis but found no evidence for a direct role in this process. Vax1 is not expressed in the developing palate and mutant palatal shelves elevate above the tongue, demonstrating morphology and proliferation indices indistinguishable from wild type. However, mutant mice did have a large midline cavity originating from the embryonic forebrain situated beneath the floor of the hypothalamus and extending through the nasal cavity to expand this region and prevent approximation of the palatal shelves. Interestingly, despite strong expression of Vax1 in ectoderm of the medial nasal processes, the upper lip remained intact in mutant mice. We found further evidence of disrupted craniofacial morphology in Vax1 mutants, including truncation of the midface associated with reduced cell proliferation in forebrain neuroectoderm and frontonasal mesenchyme. Sonic hedgehog (Shh) signal transduction was downregulated in the mutant forebrain, consistent with a role for Vax1 in mediating transduction of this pathway. However, Shh was also reduced in this region, suggestive of a Shh-Vax1 feedback loop during early development of the forebrain and a likely mechanism for the underlying lobar holoprosencephaly. Despite significant associations between VAX1 and human forms of CLP, we find no evidence of a direct role for this transcription factor in development of this region in a mutant mouse model.

Characterization of the live salmonid movement network in Ireland: Implications for disease prevention and control.

Live fish movement is considered as having an important role in the transmission of infectious diseases. For that reason, interventions for cost-effective disease prevention and control rely on a sound understanding of the patterns of live fish movements in a region or country. Here, we characterize the network of live fish movements in the Irish salmonid farming industry during 2013, using social network analysis and spatial epidemiology methods, and identify interventions to limit the risk of disease introduction and spread. In the network there were 62 sites sending and/or receiving fish, with a total of 130 shipments (84 arcs) comprising approx. 17.2 million fish during the year. Atlantic salmon shipments covered longer distances than trout shipments, with some traversing the entire country. The average shipment of Atlantic salmon was 146,186 (SD 194,344) fish, compared to 77,928 (127,009) for trout, however, variability was high. There were 3 periods where shipments peaked (February-April, June-September, and November), which were related to specific stages of fish. The network was disconnected and had two major weak components, the first one with 39 nodes (mostly Atlantic salmon sites), and the second one with 10 nodes (exclusively trout sites). Correlation between in and out-degree at each site and assortativity coefficient were slightly low and non-significant: -0.08 (95% CI: -0.22, 0.06) and -0.13 (95% CI: -0.36, 0.08), respectively, indicating random mixing with regard to node degree. Although competing models also produced a good fit to degree distribution, it is likely that the network possesses both small-world and scale-free topology. This would facilitate the spread and persistence of infection in the salmon production system, but would also facilitate the design of risk-based surveillance strategies by targeting hubs, bridges or cut-points. Using Infomap community detection algorithms, 2 major communities were identified within the giant weak component, which were linked by only 4 nodes. Communities found had no correspondence with geographical zones within the country, which could potentially hinder the implementation of zoning strategies for disease control and eradication. Three significant spatial clusters of node centrality measures were detected, two in county Donegal (betweenness and outcloseness) and one in county Galway (incloseness), highlighting the importance of these locations as hot spots of highly central sites with a higher potential for both introduction and spread of infection. These results will assist in the design and implementation of measures to reduce the sanitary risks emerging from live fish trade within Ireland.

Amniotic fluid infection with intact membranes in relation to stillborns.

The role of transamniotic fetal infection in the presence of intact membranes has attracted widespread attention. The present study is a reexamination of the autopsy material from 145 cases of macerated stillbirth observed in the National Maternity Hospital from 1979 to 1982. The objective was to ascertain the incidence of congenital pneumonia. No more than five cases were discovered, and in only two of these was there convincing evidence that the membranes were intact. The amniotic fluid infection syndrome seemed to be of little importance in the causation of late intrauterine death.

An epidemic of venereal infection in thoroughbreds.

The clinical pattern, bacteriological investigation and subsequent treatment of a serious outbreak of venereal disease in stud farms on both sides of the Irish Sea is described. The consistency with which Bacillus proteus was isolated from infected mares and stallions was remarkable. Prompt treatment with ampicillin, to which the organism was sensitive in vitro, eradicated the disease. No local treatment was applied.

Inhibitory effect of quercetin on periodontal pathogens.

INTRODUCTION: Periodontal disease and associated bone loss can severely hinder orthodontic treatment. Actinobacillus actinomycetemcomitans (Aa) and Porphyromonas gingivalis (Pg) are bacteria which are strongly associated with this type of bone loss. Quercetin, a unique flavonoid, which is found in many common foods including apples, onions and tea may have a effect against these bacteria. AIMS: To study the effect of quercetin on the in vitro growth of periodontal pathogens Aa and Pg. MATERIAL AND METHODS: The antimicrobial effects were determined in vitro using a broth dilution assay. Aa and Pg were grown to a density of 10(7) to 10(8) cfu/mL and subsequently incubated with test solutions of quercetin at different concentrations (0.025 g/mL, 0.05 g/mL, and 0.1 g/ mL). 0.2% chlorhexidine was used as the positive control and 0.9% sodium chloride (NaCl) as the negative control. Aliquots for the growth assay were taken as soon as the solutions were mixed, and after 1, 3, 6, and 24 hours of incubation in an anaerobic chamber for Aa and Pg. Colonies appearing on the blood agar plates were visually counted after three days for Aa and 5 days for Pg. RESULTS: This study demonstrated that quercetin is a potent antimicrobial agent. When Aa and Pg were incubated with quercetin, their growth began to be inhibited at 1 hour. Aa, shows a transient inhibitory effect for 1 to 12 hours after which the antimicrobial effect gradually decreasds. With Pg, the effect increased with time and complete inhibition was achieved with concentrations of 0.1 g/mL, 0.05 g/mL and 0.025 g/mL by 24 hours. No significant difference was found between the chlorhexidine group and the quercetin solution after 24 hours of incubation. CONCLUSION: Quercetin has an inhibitory effect on Aa and Pg.

Disseminated arterial calcification associated with acardius acephalus.

Widespread arterial calcification was shown at necropsy in an infant who died at age 5 days and whose twin was acardiac. The changes resembled closely those described in idiopathic arterial calcification of infancy and the possible importance of haemodynamic factors in the production of these changes is discussed.

Traumatic intracranial haemorrhage in firstborn infants and delivery with obstetric forceps.

Exclusive of breech presentation, traumatic intracranial haemorrhage was demonstrated at necropsy on 27 occasions in 36 420 consecutive firstborn infants. All 27 were forceps deliveries. The main conclusion is that serious injury to the forecoming head at birth is almost invariably a direct effect of forceps. The relevance of this conclusion to some aspects of contemporary obstetric practice is discussed briefly.

First observation of herpes-like virus particles in northern pike, Esox lucius L., associated with bluespot-like disease in Ireland.

Circular whitish granular lesions, 5-12 mm in diameter, were observed on the skin and fins of a wild northern pike, Esox lucius, caught in a lake in the Republic of Ireland. Histological examination of the lesions revealed hypertrophied cells in the epidermis with deeply basophilic enlarged nuclei and dark-staining granular material in the cytoplasm. Transmission electron microscopy of these cells revealed naked hexagonal herpes-like virus nucleocapsids (97 +/- 7 nm) in their nuclei while the cytoplasm contained multiple aggregates of enveloped viral particles. This is the first report of herpes-like virus particles in northern pike originating outside North America, where esocid herpesvirus-1 (EsHV-1) has previously been reported. Shared clinical, histological, morphological and epidemiological findings suggest that the observed particles in this report may also be EsHV-1.

para-acetamidobenzoylglutamate is a suitable indicator of folate catabolism in rats.

The amount of biologically active folate excreted in the urine corresponds to a small fraction of the recommended dietary allowance, suggesting that a large amount of folate is excreted as its catabolites. A strategy of assessing folate requirement by measuring the daily urinary levels of products of folate catabolism depends on the demonstration of an exclusive mechanism of breakdown as well as a suitable marker of the catabolic process. Rats were given [3H] and [14C]folic acid by gastric intubation daily for 10 d to simulate normal dietary intake of the vitamin. Total urine was collected throughout this period as well as for the following 10 d. Reverse-phase HPLC of the radiolabeled urinary products revealed the presence of a variety of intact folates as well as products of C9-N10 scission of the folate molecule, pteridines, para-aminobenzoylglutamate and para-acetamidobenzoylglutamate. We detected no other N10-containing catabolites, nor did we find the oxidized folate derivative '4 alpha-hydroxy-5-methyltetrahydrofolate'. Of all the urinary folate metabolites, only para-acetamidobenzoylglutmate persisted at high levels up to 10 d after radiolabel treatment was withdrawn. We conclude that folate catabolism occurs exclusively through C9-N10 cleavage and that measurement of urinary para-acetamidobenzoylglutmate provides a suitable indicator of daily folate turnover.