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IntroductionCharacterising the shapes, dimensions and overall numbers of fragments produced by explosive devices is important for determining methods of potential mitigation, such as personal armour. The aim of this investigation was to compare the mass of excised fragments with that predicted from CT to ascertain the validity of using such an approach to measure retained fragments for multiple body areas using CT alone.Method27 retained fragments excised from consecutive patients treated at a US Role 3 Medical Treatment Facility in Afghanistan were examined. Each fragment was measured in three dimensions and the mass was obtained to estimate the density and thereby probable composition. These same excised fragments were identified radiologically and their predicted masses calculated and compared with the known masses with a paired t-test. The total numbers of retained fragments in each of four body areas for 20 casualties were determined radiographically and the mass of the largest fragment in each body region estimated.ResultsExcised fragments were most commonly metallic (17/27, 63%), with masses ranging from 0.008 to 37.6 g. Mean mass predicted from CT was significantly different from than that measured (p=0.133), with CT underestimating true mass by 5%–17%. 889/958 (93%) retained fragments appeared metallic on imaging, with the most commonly affected body areas being the torso and upper extremity (45% of casualties).ConclusionsPredicting the mass of metallic fragments from CT was possible with an error margin of up to 5%, but was less accurate for non-metallic fragments such as stone. Only 3% of fragments were removed through debridement or purposeful excision; these were not just the largest or most superficial. This suggests that future retrospective analysis of the dimensions and predicted masses of retained fragments in larger casualty cohorts of service personnel is potentially feasible within a small margin of error.

Background Recent evidence suggests that medication-related osteonecrosis of the jaw (MRONJ) can be caused by a number of anti-resorptive and anti-angiongenic agents not limited to bisphosphonates. A working knowledge of these medications is important for dental practitioners.Methods A total of 129 general dental practitioners (GDPs) were surveyed regarding their awareness of MRONJ and its causes.Results More than 90% of the GDPs sampled were unaware of anti-resorptive and anti-angiogenic medications other than bisphosphonates that had the potential to cause MRONJ. Just over 40% of the sampled GDPs were confident to treat patients on oral bisphosphonates in primary care. Much of the reluctance to manage these patients was due to lack of accessible guidelines and unclear protocols.Conclusions The results demonstrate GDP attitudes to patients taking bisphosphonates and highlight how further education is needed to increase confidence to perform simple exodontia amongst this cohort of patients in a primary care setting. As there continues to be a shift to providing dentoalveolar services in primary care, we must ensure that those performing the treatments have a greater understanding of potential MRONJ risks and have guidance as to when to refer.

Exercise-induced pulmonary hemorrhage (EIPH) is common in horses following intense exertion, occurring in up to 75% of racing Thoroughbreds and Standardbreds. In spite of this, the pathogenesis of EIPH is poorly understood. In 7 racing Thoroughbred horses with EIPH, 6 sections were collected from the left and right lung, representing the cranial, middle, and caudal region of the dorsal and ventral lung (84 sites total). Grossly, both right and left lungs had numerous dark brown to blue-black foci along the caudodorsal visceral pleura. Tissue sections were stained with hematoxylineosin, Masson's trichrome, and Prussian blue. Verhoeff Van Gieson and immunohistochemistry for α-smooth muscle actin were used to assess the pulmonary vasculature. Histologic scores (HS = 0–3) were assigned to each region/slide for the presence and severity of 5 findings: interstitial fibrosis, hemosiderin accumulation, pleural/interlobular septal thickness, arterial and venous wall thickness, and evidence of angiogenesis (maximum cumulative HS = 15). Thirty-nine of the 84 (46%) sections were histologically normal (HS = 0); 33/84 (39%) were mildly to moderately affected, with small amounts of hemosiderin and fibrosis (HS = 1–9) while 12/84 (14%), primarily from the dorsocaudal lung, had severe vascular remodeling, fibrosis, and hemosiderin accumulation (HS = 10–15). In the latter, veno-occlusive remodeling of the intralobular veins colocalized with hemosiderosis, fibrosis, hypertrophy of vessels within the pleura, and interlobular septa and bronchial neovascularization. We propose that regional veno-occlusive remodeling, especially within the caudodorsal lung fields, contributes to the pathogenesis of EIPH, with the venous remodeling leading to regional vascular congestion and hemorrhage, hemosiderin accumulation, fibrosis, and bronchial angiogenesis.

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Abstract: Spray adjuvants were tested for their effects on epicuticular wax morphology, grape berry microflora and susceptibility of berries to Botrytis cinerea on Chardonnay, Shiraz and Cabernet Sauvignon cultivars. The four adjuvants used in this trial altered epicuticular wax morphology. Disintegration of the wax platelets was least for the wetter-spreader recommended for sensitive crops, and greatest for the crop oil concentrate and the activator-penetrant. Waxes did not regenerate over the season after treatment with the adjuvants. A cyprodinil/fludioxonil fungicide was effective at controlling B. cinerea infection, but when combined with an adjuvant, was less effective in the three grape cultivars. Irrespective of whether a fungicide was used, adjuvant application resulted in lower yeast and fungal populations on Chardonnay berries. There were no effects of the adjuvants on the microflora of Shiraz and Cabernet Sauvignon berries, except for the crop oil concentrate which resulted in higher bacterial populations on Cabernet Sauvignon berries. We hypothesise that spray adjuvants increased the susceptibility of grape berries to B. cinerea through epicuticular wax alteration and, in some circumstances, through the reduction of the indigenous microflora on the berry surface.

Dedicated clinics have been established for the early diagnosis and treatment of women at risk for inherited breast cancer, but the effects of such interventions are currently unproven. This second report on prospectively diagnosed inherited breast cancer from the European collaborating centres supports the previous conclusions and adds information on genetic heterogeneity and the effect of oophorectomy. Of 249 patients, 20% had carcinoma in situ (CIS), 54% had infiltrating cancer without spread (CaN0) and 26% had cancer with spread (CaN+). Five-year survival was 100% for CIS, 94% for CaN0 and 72% for CaN+ (p = 0.007). Thirty-six patients had BRCA1 mutations, and 8 had BRCA2 mutations. Presence of BRCA1 mutation was associated with infiltrating cancer, high grade and lack of oestrogen receptor (p < 0.05 for all 3 characteristics). For BRCA1 mutation carriers, 5-year survival was 63% vs. 91% for noncarriers (p = 0.04). For CaN0 patients, mutation carriers had 75% 5-year disease-free survival vs. 96% for noncarriers (p = 0.01). Twenty-one of the mutation carriers had undergone prophylactic oophorectomy, prior to or within 6 months of diagnosis in 13 cases. All but 1 relapse occurred in the 15 who had kept their ovaries, (p < 0.01); no relapse occurred in those who had removed the ovaries within 6 months (p = 0.04) Contralateral cancer was more frequently observed in mutation noncarriers, but this finding did not reach statistical significance. Our findings support the concept that BRCA1 cancer is biologically different from other inherited breast cancers. While current screening protocols appear satisfactory for the majority of women at risk of familial breast cancer, this may not be the case for BRCA1 mutation carriers. The observed effect of oophorectomy was striking. © 2002 Wiley-Liss, Inc.

Many theoretical accounts of selective attention and memory retrieval include reference to active inhibitory processes, such as those argued to underlie the negative priming effect. fMRI was used in order to investigate the areas of cortical activation associated with Stroop interference, Stroop facilitation and Stroop negative priming tasks. The most significant activation within the negative priming task was within the inferior parietal lobule, left temporal lobe and frontal lobes. Areas of cortical activation are discussed with reference to theoretical accounts of the negative priming effect.

Familial ovarian cancer clinics are a recent development and little is known about the characteristics of women who attend. One hundred and ninety-seven women with a family history of ovarian cancer completed a questionnaire prior to their initial attendance at the Familial Ovarian Cancer Clinic in Edinburgh. Issues relating to screening procedures were the most commonly cited barriers to attendance, with a proportion finding gynaecological examination embarrassing (17.0%) or uncomfortable (18.0%). Expectations of the clinic were high in terms of access to resources and information. The vast majority of women would prefer to have regular screening (94.7%) and genetic testing (93.2%) if it were available. Attitudes to prophylactic surgery and chemoprevention were more diverse, but would be considered by 54.3% and 43.9% of respondents respectively. Although the current screening procedure for ovarian cancer is of unproven efficacy, a high proportion of women believed in its ability to reduce mortality (77.9%) and to detect tumours at an early stage (65.8%). There was a trend for women to believe this more strongly at follow-up. This study highlights the need to make women more aware of the limitations of current ovarian cancer screening techniques, particularly where the alternative management strategy of prophylactic surgery might otherwise be dismissed.

Eight breast cancer pedigrees with a high probability of containing individuals with the BRCA1gene mutation (odds 79·2–99·9 per cent) were identified through genetic linkage analysis using probes located within q12–22 on the long arm of chromosome 17. Some 102 female relatives were successfully typed with one or both of adjacent markers D17S588 and D17S579, and 41 were probable non-BRCA1 mutation carriers. Of the remaining 61 women classified as probable BRCA1carriers, breast cancer was diagnosed in 35. As expected from epidemiological segregation analysis studies, 13 of these had bilateral disease. Approximately two-thirds of women unaffected by malignancy and alive at the time of observation were non-BRCA1carriers. Lifetime disease penetrance of the BRCA1gene was 88 per cent and this plateau was reached earlier (by age 65 years) than that estimated in segregation analysis. The survival curve of patients with breast cancer was less steep in BRCA1gene carriers than that in the general population; 5-, 10- and 20-year survival rates unadjusted for non-cancer deaths were 83, 63 and 41 per cent respectively. The 5-year survival rate was significantly higher in BRCA1carriers than that in an age-matched Scottish population (P<0·05).

Up to 20 per cent of cases of breast cancer diagnosed in women under the age of 45 years may be caused by an autosomal dominant gene. A present difficulty is differentiation of mutation carriers from nonmutation carriers in high-risk families. Genetic linkage analysis has been used to localize a susceptibility gene (BRCA1) on chromosome 17q12-21 between markers 42D6 and MFD 188, a region 5–10 million base pairs in length. Odds in favour of linkage to this region were greater than 100 000: 1 in 15 families with breast cancer. In eight families in which the probability of linkage was above 75 (range 79·2–99·9) per cent, 19 women were identified who were at high lifetime risk of breast cancer (range 80·6–87·2 per cent) and 37 whose risk was similar to that for the general population (range 9·8–16·4 per cent). Genetic risk prediction of this kind may enable high-risk screening clinic resources to be concentrated on those most likely to benefit.

A micro culture system is described in which 2.5 × 104 human blood lymphocytes in aliquots of 100 μL are stimulated by PHA, Pokeweed, "Varidase" antigen, allogeneic small lymphocytes or mitomycin-C-treated allogeneic LCL cells. Careful regulation of the pH by a combination of bicarbonate and MOPS buffers seems to be important for detecting a response to weak stimuli. High and reproducible levels of activation by powerful stimuli (PHA and LCL cells) can be recorded from even smaller cultures (104 responding cells in 40 μL aliquots). The technique allows large numbers of replicate cultures to be set up from a single blood sample so that the time course and/or dose-response relationships can be examined for a range of differen mitogens.

This paper covers a unique program created in the United Kingdom between the MRC Cyclotron Unit and the CRC Phase I and II drug development committee to investigate the potential of tracer kinetic studies to investigate in vivo tumor and normal tissue kinetics, molecular interactions, pathways, and mechanism of action of novel anti-cancer agents. Positron emission tomography technology offers great potential in streamlining anti-cancer drug development programs, however, significant investment in new methodology and multidisciplinary teams is necessary.

The use of GCMS and FDMS to examine extracts of water before and after passage through epoxy resin lined water distribution mains has shown that many components of the resin and hardener formulations are leached into the water. Although the GCMS results indicated that the levels of some compounds leached were rapidly reduced, the FDMS results showed that other compounds were still being leached six months after relining.

Abstract: The paired prothoracic glands of the insect Rhodnius prolixus each comprise a group of about 200 structurally identical cells. The synthesis (and release) of steroid moulting hormones (ecdysteroids) by these glands is under circadian control in vivo. We monitored ecdysteroid synthesis by single glands during long-term incubations in vitro. Synthesis is rhythmic in vitro and persists in continuous darkness. Glands which are arrhythmic (from prolonged continuous light) respond to transfer to darkness in vitro with the initiation of a free-running circadian rhythm of ecdysteroid synthesis. Therefore, the glands possess a light-sensitive circadian oscillator. These properties are conventionally associated with nervous tissue of animals. It is suggested that rhythmicity is synchronized within the gland by the known structural and electrical coupling between its component cells. The glands share properties with known pacemakers such as the avian pineal. However, the glands in vivo receive input from both light cues and the cerebral neuropeptide, prothoracicotropic hormone. Rhythmic release of this neuropeptide is controlled by a second oscillator located in the brain. We conclude that the pacemaker in the endocrine system of R. prolixus comprises at least three oscillators, one in each prothoracic gland and one in the brain, which are coupled hormonally. We conclude that the prothoracic gland is an important component of the circadian system controlling development in R. prolixus and that peripheral endocrine glands may play a more active role in the generation of animal circadian organization than has been thought.

Infection of cervical epithelial cells with so-called "aggressive" subtypes of human papilloma virus (HPV) appears to be an important factor in the etiology of cervical carcinoma. However, mounting evidence suggests that additional genetic changes are required for progression to an invasive carcinoma. Functional studies have shown that human chromosome 11 contains a gene or genes capable of suppressing tumorigenicity in cell lines derived from different histopathological types of cervical carcinoma, suggesting that aberration of this gene(s) may represent at least one of the additional changes required for tumorigenic progression. To identify the likely chromosomal position of this gene(s), we have carried out a systematic genetic analysis of chromosome 11 in the primary tumors of 32 patients with cervical carcinoma. Sixteen highly polymorphic markers, 10 of which were based on simple sequence repeats typed by PCR, were used to compare matched DNA samples from noninvolved tissue and portions of tumor tissue highly enriched for neoplastic cells by the cryostat-sectioning technique. Of the 32 patients examined, 14 (44%) demonstrated clonal genetic alterations resulting in loss of heterozygosity for one or more markers. Seven of the clonal genetic alterations on chromosome 11 were specific to the long arm, and the overlap between these and other allelic deletions suggests that a suppressor gene(s) relevant to cervical carcinoma maps to chromosome 11q22-q24.

1.Ecdysis in populations ofRhodnius prolixus maintained on L:D cycles is restricted to gates of approximately 6 h in width (Fig. 1). These gates recur at 24 h intervals producing an ecdysis rhythm in the population. This rhythm of gated ecdysis occurs in all instars but has been analysed mainly using the imaginal ecdysis. The ecdysis rhythm free runs in the absence of environmental time cues with a period of 23.4 h which is temperature compensated with a Q10 of 1.04 (Fig. 3A, B). Thus the ecdysis rhythm inRhodnius is circadian.2.Rhodnius is the first hemimetabolous insect in which a circadian ecdysis rhythm has been described.3.The ecdysis rhythm is responsive to phase shifts of the L:D cycle applied before, during or after the time of PTTH release (Fig. 4). Thus the position relative to the L:D cycle of the gates for ecdysis inRhodnius is not set by the prior release of developmental neurohormones unlike the proposed mechanism controlling larval ecdysis in moths. The gate for ecdysis is susceptible to environmental manipulations up to the 24 h prior to ecdysis, suggesting that the circadian system acts at a time very close to ecdysis.

In terrestrial isopods, different sensory cues initiate reproduction and moulting, indicating that the two processes are controlled by different physiological mechanisms. A specific sensory trigger which initiates premoult is identified; it occurs well before conventional signs of premoult become evident. Specific coordinating mechanisms adjust the chronology of moulting and vitellogenesis under conditions promoting both processes. The first phase of vitellogenesis can occur either in intermoult or early premoult according to conditions and is considered to be independent of ecdysone. The second phase invariably occurs in late premoult and may be ecdysone-dependent. The relations between moulting and reproduction are regarded as separately controlled processes which interact via specific cues which coordinate and adjust the timing of the two processes. Implications of this concept are discussed.

Roughly 25% of human B–cell chronic lymphocytic leukaemias (CLL) are characterized by a chromosomal lesion involving 13q14. This region contains the retinoblastoma gene (RB1). We have used a variety of techniques to determine whether RB1 or some other locus is the critical region in 11 cases of low grade B–cell malignancy (mainly CLL), all with deletions or translocations involving 13q14. In all cases, except the one with minimal disease, there was deletion or a structural lesion in the region of D13S25, with at least 4 cases showing homozyogous disruption. We conclude that D13S25 lies close to a tumour suppressor locus whose inactivation contributes to the initiation or progression of low grade B–cell malignancy. This locus is located at least 530 kilobases telomeric to RB1.

The location of the photoperiodic mechanism controlling the production of the sexual and parthenogenetic morphs by apterous parents was examined by selectively injuring the brain with an R.F. microcautery. Lesions destroying the Group I neurosecretory cells (NSC) in the protocerebrum abolished the response to changed daylength. Extensive damage to other NSC Groups, to the compound eyes and optic lobes was without effect. It is concluded that the Group I NSC are the effectors, secreting a virginoparapromoting substance; in its absence only oviparae are produced. Areas slightly lateral to the Group I NSC are also required for the long-day response, indicating that this is the probable site of the neuronal photoperiodic clock which regulates the release of neurosecretory material (NSM) from the Group I cells.

DA6.231 and DA6.164 are mouse monoclonal antibodies that immunoprecipitate HLA-DR-like p34,29 glycoprotein dimers from surface- and metabolically-labeled cells. On lymphoblastoid cell lines the distribution of the 231 epitope is completely nonpolymorphic, while the 164 epitope is present on all cells except on those that are DR7 homozygous. Binding-inhibition studies show that the 231 and 164 epitopes are spatially close to each other when present on the same molecule. The mutual inhibition pattern and the absence of the 164 epitope from the 231+ cells of a few leukemia patients suggest, however, that 231 and 164 epitopes are not invariably present together. Most DR-positive cells possess 231- 164+ and 231+ 164- class 11 molecules in approximately a 2:1 ratio. This has been confirmed by immune depletion studies. Thus DA6.231 appears to define a supralocus epitope. The 164 epitope may be a marker for a subset of class 11 molecules exhibiting differential expression on various cell types immortalized by malignant transformation.

Human somatic cell hybrids were generated from fusions between a tumorigenic B-cell line, and mononuclear cells from a patient with low-grade B-cell lymphoma in which the neoplastic cells largely corresponded to cells at an intermediate stage of differentiation. The resulting hybrids and the parent cells were immunophenotyped, karyotyped and genotyped in an effort to determine whether the stage of B-cell development of the fusion partners was important in the suppression of malignancy. The majority of hybrids demonstrated suppression of tumorigenicity as measured in immunodeprived mice. Chromosome markers and immunoglobulin gene rearrangements found in the patient’s neoplastic cells were also present in several of the hybrids. One of the tumorigenic hybrids retained specific chromosomes also found in the non-tumorigenic hybrids, but demonstrated an immunophenotype and genotype possibly associated with a subset of early B-cells. In the non-tumorigenic hybrids that retained most of the chromosomes from both parents there was evidence of plasmacytoid differentiation. These results suggest that the ability of B-lymphocytes to suppress malignancy in human lymphoid hybrids may be dependent on the corresponding stage of normal B-cell ontogeny, and that suppression is associated with differentiation.

Prothoracicotropic hormone (PTTH) is the central cerebral neurohormone in insect development. Its release has been believed for decades to be confined to one (or two) critical moments early in each developmental stage at which time it triggers prolonged activation of the prothoracic glands to synthesize and release the steroid molting hormones (ecdysteroids), which elicit developmental responses in target tissues. We used an in vitro assay for PTTH released from excised brains of the bug Rhodnius prolixus and report that release of PTTH does occur at the expected time on day 6, but that this release is merely the first in a daily rhythm of release that continues throughout most of the 21 days of larval-adult development. This finding, together with reports of circadian control of ecdysteroid synthesis and titer throughout this time, raises significant challenges to several features of the current understanding of the hormonal control of insect development. New questions are raised concerning the function(s) of PTTH, its relationship with the prothoracic glands, and the significance of circadian rhythmicity throughout this endocrine axis. The significance of the reported observations derives from the set of entirely new questions they raise concerning the regulation of insect development.

This paper covers a unique program created in the United Kingdom between the MRC Cyclotron Unit and the CRC Phase I and II drug development committee to investigate the potential of tracer kinetic studies to investigate in vivo tumor and normal tissue kinetics, molecular interactions, pathways, and mechanism of action of novel anti-cancer agents. Positron emission tomography technology offers great potential in streamlining anti-cancer drug development programs, however, significant investment in new methodology and multidisciplinary teams is necessary.

The cytolethal response to treatment with prednisolone was investigated in vitro in eight human lymphoblastoid cell lines containing varying concentrations of specific cytoplasmic glucocorticoid receptors. A similar response was observed in seven of the lines irrespective of their concentration of cytoplasmic receptors and pharmacological doses of steroid, well above those required to saturate receptors in cell-free extracts, were required for a massive lethal response. One cell line derived from Burkitt's lymphoma was refractory to lethal effects even with pharmacological doses of steroid. A similar unresponsiveness to the cytolethal effect of prednisolone in vitro was observed in fresh lymphoblasts derived from patients with acute lymphoblastic leukaemia despite evidence of a satisfactory clinical response to therapy which included steroid. The resistance of human lymphoblastoid cells to treatment with glucocorticoids in vitro may result from a defect in activation subsequent to the binding of steroid to cytoplasmic receptors.

In normal fifth instar Rhodnius the cytological changes occurring in the medial neurosecretory cells (MNC) of the brain are very different before and after the ‘critical period’ for decapitation. When a decapitated insect which has reached the ‘critical period’ (8 days after feeding) is joined in parabiosis to an insect with an intact cerebral endocrine system and which has not yet reached the ‘critical period’ (1 day after feeding) the MNC of the younger insect are induced to switch over from their normal sequence of cytological changes to those characteristic of the older insect. The induced changes do not occur in normal insects of the same age or in insects joined in parabiosis to others of the same age. The nature of the changes indicates that release of stainable neurosecretory material is inhibited and its synthesis stimulated by the older insect. It is inferred that the haemolymph of insects which have reached the ‘critical period’ contains a factor which induces in the MNC an inhibition of release and a stimulation of synthesis. These are the events which occur in the MNC of normal insects at the critical period. Considerable circumstantial evidence suggests that the factor is ecdysone. It may act either directly on the brain or on the corpus allatum. Its contribution to a feedback regulation of the endocrine system controlling growth and moulting is discussed.

Summary

The carotenoid content was examined in leaf and berry tissues of grapevines (cv. Cabernet Sauvignon) grown either under ambient conditions or under a polyester film to reduce UV light by 98%. Total carotenoids in leaves were less in vines grown under the UV screen. Levels of β-carotene decreased with berry development around veraison. This effect was more pronounced in vines grown under reduced UV light. The lutein content of berries appeared to remain relatively constant with berry development, but levels were decreased under the UV screen. These observations are important for the wine industry because of the biosynthetic link between carotenoids and wine flavour and aroma compounds.