Cancer effect on periprocedural thromboembolism and bleeding in anticoagulated patients.

BACKGROUND: Patients with active cancer are often on chronic anticoagulation and frequently require interruption of this treatment for invasive procedures. The impact of cancer on periprocedural thromboembolism (TE) and major bleeding is not known. PATIENTS AND METHODS: Two thousand one hundred and eighty-two consecutive patients referred for periprocedural anticoagulation (2484 procedures) using a standardized protocol were followed forward in time to estimate the 3-month incidence of TE, major bleeding and survival stratified by anticoagulation indication. For each indication, we tested active cancer and bridging heparin therapy as potential predictors of TE and major bleeding. RESULTS: Compared with patients without cancer, active cancer patients (n=493) had more venous thromboembolism (VTE) complications (1.2% versus 0.2%; P=0.001), major bleeding (3.4% versus 1.7%; P=0.02) and reduced survival (95% versus 99%; P<0.001). Among active cancer patients, only those chronically anticoagulated for VTE had higher rates of periprocedural VTE (2% versus 0.16%; P=0.002) and major bleeding (3.7% versus 0.6%; P<0.001). Bridging with heparin increased the rate of major bleeding in cancer patients (5% versus 1%; P=0.03) without impacting the VTE rate (0.7% versus 1.4%, P=0.50). CONCLUSIONS: Cancer patients anticoagulated for VTE experience higher rates of periprocedural VTE and major bleeding. Periprocedural anticoagulation for these patients requires particular attention to reduce these complications.

Predictors of major bleeding in peri-procedural anticoagulation management.

BACKGROUND: Appropriate periprocedural management for chronically anticoagulated patients requires assessment of patient-specific thrombosis and bleeding risks. However, predictors of post-procedure bleeding are unknown. OBJECTIVES: To determine the 3-month cumulative incidence and independent predictors of peri-procedural bleeding in chronically anticoagulated patients requiring temporary warfarin interruption for an invasive procedure. METHODS: In a protocol driven, cohort study design, all patients referred to the Mayo Clinic Thrombophilia Center for peri-procedural anticoagulation management (1997-2007; n = 2182), were followed forward in time to determine the 3-month cumulative incidence of peri-procedural bleeding (Kaplan-Meier product limit) and potential predictors of bleeding (Cox proportional hazards). Decisions to 'bridge' with low-molecular-weight heparin were based on estimated thromboembolism and bleeding risk. RESULTS: Indications for chronic anticoagulation included venous thromboembolism (38%), atrial fibrillation (30%) and mechanical heart valves (27%). Of these, 1496 (69%) patients received bridging therapy. The 3-month cumulative incidence rates of major and overall bleeding were 2.1% and 5.1%, respectively. Major bleeding occurred more frequently in patients receiving bridging therapy (3% vs. 1%; P = 0.017). Independent predictors (hazard ratio; 95% confidence interval) of major bleeding included mitral mechanical heart valve (2.2; 1.1-4.3), active cancer (1.8; 1.0-3.1), prior bleeding history (2.6; 1.5-4.5) and re-initiation of heparin therapy within 24 h after the procedure (1.9; 1.1-3.4). CONCLUSION: Factors predisposing to peri-procedural bleeding are primarily patient-specific. Premature heparin re-initiation is an avoidable provider-specific variable to consider.

A genetic association study of 5-HTT LPR and GNbeta3 C825T polymorphisms with irritable bowel syndrome.

A pharmacogenetic study suggests the 5-HTT LPR polymorphism predicts response to alosetron, and another study describes a possible association of the GNbeta3 C825T polymorphism with IBS in patients with dyspepsia. We performed a case-control association study to determine whether these polymorphisms are associated with irritable bowel syndrome (IBS). The study aim was to compare allele and genotype frequencies between cases and controls for the 5-HTT LPR and the GNbeta3 C825T polymorphism. Cases were 50 GI outpatients; controls were 53 General Medicine outpatients matched to cases for age, gender and race at a major medical centre. Participants completed a questionnaire and donated blood. DNA was genotyped using polymerase chain reaction based assays. Eighty-two per cent of cases met Rome II criteria for IBS: 12% constipation-, 46% diarrhoea-, and 42% mixed-IBS. Genotype and allele frequencies for both polymorphisms did not differ between cases and controls. However, the allele frequency of the short (S) allele of the 5-HTT LPR polymorphism was greater in those with mixed-IBS compared with controls (68%vs 45%, P < 0.05). This study suggests that the 5-HTT LPR polymorphism may be associated with mixed-IBS, but not IBS overall. No association was observed for the GNbeta3 C825T polymorphism with IBS overall or subtypes.

A major lung cancer susceptibility locus maps to chromosome 6q23-25.

Lung cancer is a major cause of death in the United States and other countries. The risk of lung cancer is greatly increased by cigarette smoking and by certain occupational exposures, but familial factors also clearly play a major role. To identify susceptibility genes for familial lung cancer, we conducted a genomewide linkage analysis of 52 extended pedigrees ascertained through probands with lung cancer who had several first-degree relatives with the same disease. Multipoint linkage analysis, under a simple autosomal dominant model, of all 52 families with three or more individuals affected by lung, throat, or laryngeal cancer, yielded a maximum heterogeneity LOD score (HLOD) of 2.79 at 155 cM on chromosome 6q (marker D6S2436). A subset of 38 pedigrees with four or more affected individuals yielded a multipoint HLOD of 3.47 at 155 cM. Analysis of a further subset of 23 multigenerational pedigrees with five or more affected individuals yielded a multipoint HLOD score of 4.26 at the same position. The 14 families with only three affected relatives yielded negative LOD scores in this region. A predivided samples test for heterogeneity comparing the LOD scores from the 23 multigenerational families with those from the remaining families was significant (P=.007). The 1-HLOD multipoint support interval from the multigenerational families extends from C6S1848 at 146 cM to 164 cM near D6S1035, overlapping a genomic region that is deleted in sporadic lung cancers as well as numerous other cancer types. Parametric linkage and variance-components analysis that incorporated effects of age and personal smoking also supported linkage in this region, but with somewhat diminished support. These results localize a major susceptibility locus influencing lung cancer risk to 6q23-25.

Familial segregation of venous thromboembolism.

BACKGROUND: Venous thromboembolism (VTE) is postulated as a complex disease, but the heritability and mode of inheritance are uncertain. OBJECTIVE: To determine if VTE (i) segregates in families; (ii) is attributable to inheritance, shared environment, or both; and (iii) the possible mode of inheritance. PATIENTS AND METHODS: In a family-based study of relatives from 751 probands (60% female) with objectively diagnosed VTE (without cancer), we performed complex segregation analyses corrected for mode of ascertainment, considering age-specific, non-gender- and gender-specific liability classes under Mendelian and non-Mendelian assumptions. We tested 12 models categorized into four model sets: (i) sporadic (assumes no genetic effect); (ii) Mendelian inheritance of a major gene (including dominant, additive, recessive or codominant classes); (iii) mixed model (Mendelian inheritance including the same four classes plus the effect of polygenes); and (iv) non-Mendelian. RESULTS: Among the 16 650 relatives, 753 (48% female) were affected with VTE, of whom 62% were first-degree relatives. The sporadic model was rejected in both non-gender- and gender-specific liability class analyses. Among the remaining gender-specific models, the unrestricted (non-Mendelian) inheritance model was favored with an estimated heritability of 0.52. Among the Mendelian models, the dominant mixed model was preferred, with an estimated heritability and major disease allele frequency of 0.62 and 0.25, respectively, suggesting an effect of several minor genes. CONCLUSION: A multifactorial non-Mendelian inheritance model was favored as the cause for VTE, while a model postulating a purely environmental cause was rejected. VTE is probably a result of multigenic action as well as environmental exposures.

Direct-Sun column ozone retrieval by the ultraviolet multifilter rotating shadow-band radiometer and comparison with those from Brewer and Dobson spectrophotometers.

A methodology for direct-Sun ozone retrieval using the ultraviolet multifilter rotating shadow-band radiometer (UV-MFRSR) is presented. Total vertical column ozone was retrieved in three stations: Mauna Loa, Hawaii, in the U.S., and Regina, Saskatchewan, and Toronto, Ontario, in Canada, from direct solar irradiances of the UV-MFRSR at 325-, 305-, 332-, and 311-nm channels (2-nm FWHM). The total uncertainty of ozone retrievals in this study is +/-2.0%. For Mauna Loa the mean ratios of the UV-MFRSR column ozone retrievals to the collocated Dobson and Brewer were 0.998 and 0.986 between May and September of 1999. The mean ratio of UV-MFRSR retrievals to the collocated Brewer retrievals was 1.012 in Toronto between April and August of 1999, and the mean ratio of retrievals of the UV-MFRSR to the collocated Brewer was 0.988 in Regina between June and September of 1999. Total vertical column ozone values for solar zenith angles of >70 degrees were not considered, because of the signal-to-noise ratio and the angular response of the instruments, and were not used in the evaluation. The advantages of total vertical column ozone retrieval using UV-MFRSR include relatively low cost, computer-controlled operation, automated calibration stability checks, and minimal maintenance. It allows for the real-time measurement of total vertical column ozone. The UV-MFRSR is being used at 28 sites across the United States and 2 sites in Canada that form the U.S. Department of Agriculture UV-B Radiation Monitoring and Research Program. This constitutes a unique network of total vertical colunm ozone measurement.

Annual and interannual behavior of solar ultraviolet irradiance revealed by broadband measurements.

This research examines the behavior of ground-level solar UV radiation as measured by eight broadband meters in the continental United States during the period from late 1994 to late 1998. The goal is to define the variability that occurs in UV irradiance over time scales ranging from one to several years. The monthly integrated irradiances, from latitude 32 degrees N to 47 degrees N, contain large annual cycles and latitudinal gradients which depend on season. Seven of the eight sites show a maximum in July, a behavior related to proximity to the summer solstice, with modifications associated with the annual cycle in column ozone. A large interannual variability in monthly integrated irradiance appears over the 4 year period studied. A comparison of corresponding months during different years shows differences in irradiance of 20% or more in one-third of the cases analyzed. When the solar zenith angle (SZA) is held fixed in the range 60-65 degrees, a substantial annual cycle in UV irradiance remains where the maximum monthly mean irradiance is 1.4-1.9 times the minimum, depending on location. Furthermore, the annual cycle at fixed SZA is not in phase with the normal seasonal cycle. Maximum irradiances at fixed SZA tend to occur in the October to December period, while minima cluster in April through July. The annual cycle in ozone, with maximum column values in spring and minima in autumn, explains the general character of the fixed-SZA data, although changes in cloudiness are significant contributors to interannual variability.

Chorion formation and ultrastructure of the egg of the cat flea (Siphonaptera: Pulicidae).

Oocyte development in adult female cat fleas, Ctenocephalides felis (Bouché), was studied by light and electron microscopy to determine the formation and ultrastructural morphology of the eggshell. As oocytes develop, somatic follicle cells from the lining of the ovariole migrate around the oocytes. The follicle cells produce electron-dense granules that form the vitelline membrane around the developing oocyte. Subsequently, electron-lucent granules containing an electron-dense core (precursors of the chorion) are produced from the rough endoplasmic reticulum that appear as dilated and clear linear clefts in the cytoplasm of the follicle cells. Exocytosis and coalescence of the granules around the oocyte as the follicle cells disintegrate give rise to the chorion. The chorion was found to consist of 4 distinct layers. The external surface of the egg shell consists of a particulate layer approximately 760 nm thick, composed of an electron-lucent layer of widely dispersed granules. Embedded in this layer are electron-dense spheres that project above the surface of this granular layer. Beneath this outermost layer is a band of electron-dense material, consisting of densely packed granules and is half as thick as the outer particulate layer. The 3rd layer consists of relatively thick, weakly laminated chorion, with a felt-like appearance due to a meshwork of microfibrils. Projections of this network of microfibrils form pillars that attach this layer to a thin relatively compact 4th or basal layer. The pillars and the air-filled cavities lying between the 3rd and 4th chorionic layers constitute the chorionic meshwork known as the palisades or trabecular layer that form the major respiratory organ of the eggshell. The trabecular layer is connected to the external environment by means of the lateral and anterior aeroplyes. The vitelline membrane lies between the chorion and oocyte and is a granular, uniform, moderately electron-dense layer measuring approximately 260 nm thick. The micropyle at the posterior of the flea egg consists of a rosette of 50-80 apertures and possesses an internal electron-dense plug between the chorion and the vitelline membrane. An aeropyle at the anterior end of the egg consists of a rosette of 40-50 apertures. An inconspicuous aeropyle appears as a cluster of hexagonal or polygonal-shaped plaques on the lateral surface of the chorion. Each plaque contains 3-8 pores.

Comparison of column ozone retrievals by use of an UV multifilter rotating shadow-band radiometer with those from Brewer and Dobson spectrophotometers.

The U.S. Department of Agriculture UV-B Monitoring Program measures ultraviolet light at seven wavelengths from 300 to 368 nm with an ultraviolet multifilter rotating shadow-band radiometer (UV-MFRSR) at 25 sites across the United States, including Mauna Loa, Hawaii. Column ozone has been retrieved under all-sky conditions near Boulder, Colorado (40.177 degrees N, 105.276 degrees W), from global irradiances of the UV-MFRSR 332- and 305-nm channels (2 nm FWHM) using lookup tables generated from a multiple-scattering radiative transfer code suitable for solar zenith angles (SZA's) up to 90 degrees. The most significant sources of error for UV-MFRSR column ozone retrievals at SZA's less than 75 degrees are the spectral characterizations of the filters and the absolute calibration uncertainty, which together yield an estimated uncertainty in ozone retrievals of +/-4.0%. Using model sensitivity studies, we determined that the retrieved column ozone is relatively insensitive (<+/-2%) to typical variations in aerosol optical depth, cloud cover, surface pressure, stratospheric temperature, and surface albedo. For 5 months in 1996-1997 the mean ratio of column ozone retrieved by the UV-MFRSR divided by that retrieved by the collocated Brewer was 1.024 and for the UV-MFRSR divided by those from a nearby Dobson was 1.025. The accuracy of the retrieval becomes unreliable at large SZA's of more than 75 degrees as the detection limit of the 305-nm channel is reached and because of overall angular response errors. The UV-MFRSR advantages of relatively low cost, unattended operation, automated calibration stability checks using Langley plots, and minimal maintenance make it a unique instrument for column ozone measurement.

Electron microscopic investigation of the effects of diabetes mellitus on the Achilles tendon.

Fine structural changes in the Achilles tendons of patients with long-term diabetes mellitus were investigated. All patients had clinical and electrophysiological evidence of diabetic neuropathy and had ulceration and/or Charcot neuroarthropathy. Several differences between tendons of diabetic (n = 12) and nondiabetic (n = 5) individuals were observed by electron microscopy. In diabetics, these differences included increased packing density of collagen fibrils, decreases in fibrillar diameter, and abnormal fibril morphology. In one diabetic patient, individual collagen fibrils were tightly apposed so that many areas of tendon appeared as a single mass of closely adhering fibrillae. In addition, foci in which collagen fibrils appeared twisted, curved, overlapping and otherwise highly disorganized were common in specimens from most patients (11 of 12). These morphologic abnormalities in the Achilles tendons of diabetics appear to reflect a poorly known process of structural reorganization that may be the result of nonenzymatic glycation expressed over many years. Such structural changes could contribute to the tightening of the Achilles tendor a phenomenon consistent with clinical observations of extreme shortening of the Achilles tendon-gastrocnemius-soleus complex common in advanced diabetic neuropaths. In patients with diabetic neuropathy, tendon shortening causes severe equinus that may precipitate serious ulceration, stress fractures, and Charcot collapse of the foot. However, in nondiabetics, the fine structure of the Achilles tendon appears normal, consistent with the finding that the ultrastructural changes result from diabetes rather than neuropathy.

Human neutrophils store type II 14-kDa phospholipase A2 in granules and secrete active enzyme in response to soluble stimuli.

Although "secretory" type II 14-kDa phospholipase A2 (sPLA2) activity has been described in neutrophils, direct evidence of enzyme secretion has been elusive. We have used immunogold electron microscopy with polyclonal and monoclonal antibodies to sPLA2 to demonstrate localization of the enzyme to granules of resting human neutrophils and translocation to phagolysosomes. Soluble stimuli such as calcium ionophore A23187 stimulate loss of cell-associated enzymatic activity. Supernatant fluids from stimulated neutrophils lack measurable PLA2 but contain proteases which inactivate exogenous sPLA2. The use of alpha-1-antitrypsin as a protease inhibitor permitted this first demonstration of secretion of PLA2 activity from stimulated human neutrophils.

Neural regeneration and neuronal migration following injury. I. The endocrine hypothalamus and neurohypophyseal system.

Central to this investigation are several basic hypotheses that are designed to test the role of nitric oxide (NO) in the complex process of central regeneration and plasticity in a well established model system of the mammalian brain. We have employed histochemical techniques at the light and ultrastructural level coupled with correlative scanning electron microscopy, immunoelectron microscopy, and in situ hybridization in order to determine the functional significance of the increased expression of nitric oxide synthase (NOS) in neurons of the supraoptic (SON) and paraventricular (PVN) nuclei which accompanies regeneration of their axotomized neurites following hypophysectomy. The aim of this investigation was to determine the potential role and temporal up-regulation of NOS in this basic regenerative process and to establish the ultrastructural and neuroanatomical correlates during critical periods of regeneration and regrowth of SON and PVN axons following hypophysectomy in the endocrine hypothalamus of the rat. Our data support the hypothesis that NO may serve as a second messenger molecule that may act in some fashion to govern not only the process of central regeneration and regrowth of magnocellular (SON/PVN) axons into the median eminence, neural stem, and neural lobe (the neurohypophyseal system) but may also influence the regeneration of neurites into new neuroanatomical domains such as the adjacent lumen of the third cerebral ventricle. We have demonstrated a distinct temporal relationship between injury (axotomy) of SON/PVN axons and the establishment of new neurovascular zones following hypophysectomy with the up-regulation of NOS. This up-regulation appears to correlate well with successful regeneration in the mammalian neurohypophyseal system. We have also successfully inhibited axonal regeneration with the use of nitroarginine, a competitive antagonist of NO. NOS up-regulation attendant to regeneration of SON and PVN axons may have inestimable clinical implications, particularly with respect to closed head injury and cerebral contusion that involves the mechanical shearing of the infundibular stalk. In addition, this investigation has reaffirmed that large numbers of bona fide neurons migrate and emerge upon the floor of the adjacent third cerebral ventricle shortly following hypophysectomy (within 2 weeks). The origin and mechanisms of neuronal migration and plasticity following hypophysectomy are the subject of interpretation and discussion in this investigation.

Propellant-driven aerosols of functional proteins as potential therapeutic agents in the respiratory tract.

Aerosols of respirable-sized particles of functional proteins were delivered by volatile propellant from metered-dose aerosol canisters. The enzyme alkaline-phosphatase and a monoclonal antibody were lyophilized with surfactant and suspended in the aerosol propellant dimethylether. As much as 20 micrograms of functional protein, assessed by enzyme function or antibody binding activity, was delivered per 40 microliters of released propellant. Up to 25% of the protein was of respirable size (< or = 4 microns mass median aerodynamic diameter) when aerosolized proteins were sampled with a Casella cyclone. Respirable particles were derived from visible surfactant/protein complexes suspended in the liquified propellant and from propellant-soluble, nonsedimentable, surfactant/protein molecules that are probably reverse micelles. 10-14 days of propellant exposure in dimethylether increased protein solubility in the propellant, increased the total protein aerosolized and maintained or increased the quantity of respirable-sized protein molecules, as compared to the day aerosol vials were charged with propellant. Scanning electron microscopic studies of the respirable-sized protein/surfactant particles showed that they ranged in size from 0.07 to 3.25 microns in diameter, and they appeared to be chain aggregates of spherical subunits, 0.11 to 0.93 microns in diameter. This structural motif was common to both proteins. The possibility of delivering immunizing antigens, cytokines, passive antibodies and other therapeutic proteins to the respiratory tract using propellant-driven aerosols is discussed.

Enhanced larval cyst growth of Echinococcus multilocularis in praziquantel-treated jirds (Meriones unguiculatus).

Jirds (Meriones unguiculatus) inoculated intraperitoneally with cystic material of Echinococcus multilocularis were given daily oral treatments of praziquantel at 300 mg/kg of body weight (bw) or dimethyl sulfoxide vehicle for five-day treatment regimens starting at 29 days postinoculation (PI) up to 69 days PI. At 39 or 49 days PI, the growth of the larval cystic mass (LCM) in jirds following a single or two five-day treatment regimens was significantly enhanced (P < 0.05) by 129.0% (2.3-fold) or 102.9% (2.0-fold), respectively. At 59 or 69 days PI following three or four five-day treatments with praziquantel, LCM growth was enhanced by 47.8% (1.5-fold) and 44.1% (1.4-fold), respectively, but was no longer significantly different than that in control jirds. A single five-day treatment on 29-33 days PI (with necropsy at 69 days PI) significantly enhanced the growth of the LCM by 87.6% (1.9-fold). Parasites from praziquantel treatment regimens examined ultrastructurally showed consistent damage to the germinal membrane evidenced by vacuolization and rupture of syncytial cytoplasm, rupture and coalescence of the electron-lucent vesicles just below the microvilli of the tegumental surface, and swelling and rounding of mitochondria. At 39 days PI, increased blebbing of the germinal membrane into the lumen of the LCM in praziquantel-treated animals was observed by scanning electron microscopy. The treatment-induced blebs were identified as nucleated germinal cells by transmission electron microscopy and appeared to be responsible for metastasis and enhanced growth of the LCM. Although praziquantel damaged the ultrastructural integrity of the LCM, treatment failed to inhibit larval cyst growth or protoscolex development.(ABSTRACT TRUNCATED AT 250 WORDS)

Development studies of Aurelia (jellyfish) ephyrae which developed during the SLS-1 mission.

Aurelia polyps (scyphistomae) and ephyrae were exposed to microgravity for nine days aboard the space shuttle during the SLS-1 mission. During strobilation, polyps segment transversely and each segment develops into an ephyra. Polyps were induced to strobilate at 28 degrees C, using iodine or thyroxine, at L(Launch)-48h, L-24h, and L+8h. Ephyrae developed in the groups tested in space and on Earth. The number of ephyrae formed per polyp was slightly higher in the L+8h groups as compared with those induced at L-24h and L-48h. On Earth, iodine is used by jellyfish to synthesize jellyfish-thyroxine (Jf T4), needed for ephyra production. Since iodine-treated polyps strobilated and formed ephyrae in space, it appears that jellyfish can synthesize Jf-T4 in space. Indeed, two groups of polyps not given inducer formed ephyrae [correction of ephryae] in space, presumably due to enhanced Jf-T4 synthesis, utilization or accumulation. Some ephyrae that formed in space were also fixed in space on Mission Day (MD) 8; others were fixed post-flight. Examination of living ephyrae with the light microscope and fixed ones with the Scanning and Transmission Electron Microscopes revealed that those which developed in space were morphologically very similar to those which developed on Earth. Quantitation of arm numbers determined that there were no significant differences between space and Earth-developed ephyrae. Pulsing abnormalities, however, were found in greater numbers (18.3%) in space-developed ephyrae than in Earth-developed controls (2.9%). These abnormalities suggest abnormal development of the graviceptors, the neuromuscular system, or a defect in the integration between these systems in apparently microgravity-sensitive animals.

Radial glial interaction with cerebral germinal matrix capillaries in the fetal baboon.

The occurrence of intraventricular hemorrhage (IVH) is a frequent problem in premature infants delivered between 24 (60%) and 32 weeks (80%) of gestation, a time during which the germinal matrix (GM) is prominent over the head of the caudate nucleus. Most IVH arises from the GM and it has been proposed that an important factor in the pathogenesis of IVH is a weakness of GM capillary walls due to deficient support by surrounding immature glial cells. The purpose of this study was to examine the glial-capillary interaction in the GM of fetal baboons sacrificed at 100 days (54%) gestation, a stage of GM development comparable to that during which human neonatal IVH occurs. Brains from a later gestational stage (162 days, 88%), after GM involution, were also examined. At 100 days of gestational age, the GM was prominent over the head of the caudate and contained vimentin positive, but not glial fibrillary acidic protein positive, radial glial cells which formed endfeet on capillaries in the region. Ultrastructurally, all the GM capillaries examined from this gestational time had complete, continuous endothelia marked by few pinocytotic vesicles and prominent tight junctions. The endothelial cells rested upon uninterrupted basement membranes which were contacted by clearly identifiable glial endfeet. These data show that GM capillaries have morphologies typical of CNS capillaries and suggest that the capillary immaturity within the GM is not a major contributing factor to IVH.

Absence of ovicidal effects of fenoxycarb in the tick Ixodes dammini as observed by light, scanning, and transmission electron microscopy.

Freshly oviposited eggs from fed females of the northern deer tick Ixodes dammini were divided into two groups--untreated controls and fenoxycarb-exposed ova. The level of fenoxycarb exposure in the experimental group was equal to a concentration that proved 100% lethal in the cat flea, Ctenocephalides felis (Marchiondo et al. 1990). Both groups were allowed to develop with samples taken at 48 and 144 h for examination by light microscopy, scanning electron microscopy, and transmission electron microscopy. No disruption of the stages of tick embryological development was observed when specimens were examined by these methods. Eggs not sampled for light microscopy or scanning or transmission electron microscopy during development were allowed to hatch. The resulting larvae were fully developed and motile in both the control and experimental conditions, further supporting the conclusion that embryological development of I. dammini is not disrupted by concentrations of fenoxycarb which would be practical in the field.

Derivation of total ozone abundance and cloud effects from spectral irradiance measurements.

We describe a method to infer total ozone abundance and effective cloud transmission from global (diffuse plus direct) spectral irradiance measurements taken at the Earth's surface. The derivation of total ozone abundance relies on the comparison of measured irradiance ratios at two wavelengths in the UV part of the spectrum with a synthetic chart of this ratio computed for a variety of ozone abundances. One of these wavelengths should be appreciably absorbed by ozone (e.g., 305 nm) compared with the other one (e.g., 340 nm). This synthetic ratio (and therefore also the inferred total ozone abundance) is insensitive to the value of the surface albedo used in the model computations. Comparison with independent in situ and remote (from ground and space) determinations of total ozone abundance shows that measurements of global irradiances provide a reliable means of inferring the total column ozone amount for clear as well as cloudy sky conditions. Computer simulations are used to demonstrate that the ozone abunance inferred from global irradiance measurements is quite insensitive to cloud effects, whereas the use of the scattered irradiance only or the zenith sky intensity (measured routinely in the Dobson network on overcast days) requires substantial corrections for cloud effects. Effective cloud transmission is estimated from the data by comparing the measured irradiance at a wavelength where ozone absorption is minimal (e.g., 350 nm) to the clear-sky value. Irradiances generated by a plane-parallel radiation model as a function of cloud optical thickness are used to estimate an equivalent stratified cloud optical depth. These estimates of cloud transmission and optical depth are sensitive to ground reflection, implying that the accurate determination of cloud attenuation requires precise knowledge of the surface albedo.

Ovicidal and larvicidal modes of action of fenoxycarb against the cat flea (Siphonaptera: Pulicidae).

The mode of action of the insect growth regulator, fenoxycarb, on embryogenesis of cat flea eggs, Ctenocephalides felis (Bouché), was evaluated biologically and morphologically. Newly oviposited flea eggs were aged for 0, 3, 6, 12, 24, 48, or 72 h and exposed to fenoxycarb (1.1 micrograms/cm2) on filter paper disks for 0 (60 s), 2, 4, 8, 12, or 24 h at 23 +/- 1 degree C and 70 +/- 3% RH. Following exposure, samples of flea eggs were processed for microscopic examination and seeded onto carpet swatches containing flea-rearing medium in order to assess egg hatch, and larval, pupal, and adult development. Fenoxycarb exhibited embryocidal activity against eggs in early blastoderm formation, blastokinesis, and advanced larval development up to hatching. The ovicidal effect of fenoxycarb was not restricted to any specific developmental stage of embryogenesis, and no significant relationship was found between duration of exposure and lethal or inhibitory effects. Indeed, exposure for as little as 60 s produced a lethal inhibition of embryonic development. Conventional microscopy and ultrastructural observations of flea eggs exposed to fenoxycarb showed extensive cellular and tissue damage of the developing embryos, including membrane lysis, burst cells, pycnotic nuclei with coalesced and clumped heterochromatin, swollen and ruptured mitochondria, cellular autolysis, and collapse and discoloration of the eggshell. Fenoxycarb also exhibited larvicidal activity against newly emerged and 24-h-old flea larvae. The midguts of larvae exposed to fenoxybarb appeared disrupted and distorted with large gaps. These data document the ovicidal and larvicidal modes of action of fenoxycarb against the cat flea.

Distinguishing between scar and recurrent herniated disk in postoperative patients: value of contrast-enhanced CT and MR imaging.

Twenty patients with failed back surgery syndrome were analyzed prospectively with MR imaging. In addition, 10 of these patients were analyzed with high-dose contrast-enhanced CT or gadopentetate dimeglumine-enhanced MR imaging. Imaging results were compared with surgical and pathologic findings in all cases. In the 10-patient subset, abnormal epidural soft-tissue specimens were also assessed with light and electron microscopy for vascular density, size of the extracellular space, and collagen orientation and thickness. The average vascular density of epidural fibrosis on light microscopy was found to be 1.19%; the average size of the extracellular space on electron microscopy was 4.29%. Scar 4 months of age or less had a larger extracellular space than did older scar; high- (grade 4 or 5) intensity scar had a larger extracellular space than did less intense scar on long TR/short TE images. Scar 1 year old or less enhanced more intensely on CT than did older scar. The MR signal intensity and CT enhancement characteristics of epidural scar were also found to differ according to epidural location. The percentage of scar that was hyperintense on long TR/TE images was as follows: anterior, 82%; lateral recess, 70%; lateral, 47%; and posterior, 20%. However, no relationship was found between the degree of CT enhancement of scar and vascular density. Gap junction status and extracellular space size, therefore, are more important than vascular density in predicting the degree of enhancement. The accuracy of contrast-enhanced CT and unenhanced MR in separating scar from herniated nucleus pulposus is 80%. This accuracy is related to the partial overlap in imaging characteristics of scar and recurrent herniated nucleus pulposus.