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Gefapixant is a P2X3 receptor antagonist that has shown promise for the treatment of refractory and unexplained chronic cough. The aim of this study was to evaluate the efficacy of gefapixant compared with placebo after 12 weeks of treatment for refractory chronic cough or unexplained chronic cough.

The diagnosis of B-cell chronic lymphoproliferative disorders is a great challenge when made in a background of polyclonal B cells. We studied the diagnostic usefulness of aberrant CD22 expression for differentiating neoplastic from benign B cells by 4-color flow cytometry. Of 56 cases of B-cell chronic lymphoproliferative disorders, we found that neoplastic cells showed aberrant CD22 expression in 39 (70%) of 56 cases, including chronic lymphocytic leukemia, mantle cell lymphoma, marginal zone lymphoma, hairy cell leukemia, and follicular lymphoma. In 4 cases, monoclonality was detected definitively only by evaluating the immunoglobulin light chain restriction in B cells with aberrant CD22 expression because numerous polyclonal B cells were present. Aberrant CD22 expression is a useful marker for detection of monoclonal B cells admixed with numerous benign polyclonal B cells.

We wanted to evaluate whether treatment with an inhaled corticosteroid and an inhaled long-acting ß2-agonist is more effective than an inhaled corticosteroid alone for patients using as-needed albuterol who are initiating maintenance treatment.

Background: We have previously shown that omalizumab, a recombinant humanized monoclonal anti-IgE antibody, reduces asthma exacerbations and decreases inhaled corticosteroid (ICS) requirement in patients with severe allergic asthma who were symptomatic despite moderate-to-high doses of ICSs. Objective: The aim of the present study was to assess the effects of omalizumab on asthma-related quality of life (QOL). Methods: These analyses were part of a multicenter, 52-week, randomized, double-blind, placebo-controlled study assessing the efficacy, safety, and tolerability of subcutaneous omalizu-mab (≥0.016 mg/kg of IgE [in international unit per milliliter] per 4 weeks) in 525 adults with severe allergic asthma. A 16-week steroid-stable phase was followed by a 12-week steroid-reduction phase and a 24-week double-blind extension phase. The effect of treatment on asthma-related QOL was evaluated by using the Asthma Quality of Life Questionnaire (AQLQ) administered at baseline and at weeks 16, 28, and 52. Results: The 2 treatment groups were comparable in terms of baseline AQLQ scores. At weeks 16, 28, and 52, omalizumab-treated patients demonstrated statistically significant improvements across all AQLQ domains, as well as in overall score. Moreover, a greater proportion of patients receiving omali-zumab achieved a clinically meaningful improvement in asthma-related QOL during each phase of the study. Greater than 50% of both patients and investigators rated treatment similarly with omalizumab as excellent or good compared with less than 40% of placebo recipients. Conclusion: In patients requiring moderate-to-high doses of ICSs for severe allergic asthma, the measurably improved disease control afforded by add-on omalizumab therapy is paralleled by clinically meaningful improvements in asthma-related QOL. (J Allergy Clin Immunol 2003;111:278-84.)

Risedronate reduces the risk of new vertebral fractures up to 70% within 1 year of treatment in patients with osteoporosis. Both increases in bone mass and preservation of bone architecture are thought to contribute to antifracture effects. Our objectives were to determine the effects of risedronate on trabecular bone mass and architecture and to determine the relative contributions of mass and architecture to strength in the vertebra of ovariectomized (OVX) minipigs. The minipigs were OVX at 18 months of age and were treated daily for 18 months with either vehicle or risedronate at doses of 0.5 mg/kg per day or 2.5 mg/kg per day. The three‐dimensional (3D) bone architecture of the L4 vertebral cores of Sinclair S1 minipigs was evaluated by 3D microcomputed tomography (μCT). Compared with the OVX control, the vertebral bone volume (bone volume/tissue volume [BV/TV]) was higher in both treated groups (p< 0.05). The architectural changes were more significant at the 2.5‐mg/kg dose and were more prevalent at the cranial‐caudal ends compared with the midsection. At the higher dose, the trabecular thickness (Tb.Th), trabecular number (Tb.N), and connectivity were higher, and marrow star volume (Ma.St.V) and trabecular separation (Tb.Sp) were lower (p< 0.05). The trabecular separation variation index(TSVI), a new measure to approximate structural variations, was smaller in the 2.5‐mg/kg‐treated group (p< 0.05). In this group, a significant preservation of trabeculae orthogonal to the cranial‐caudal axis was confirmed by a decrease in the degree of anisotropy (DA) and an increase in the percent Cross‐strut (%Cross‐strut; p< 0.05). Both normalized maximum load (strength) and normalized stiffness of the same vertebral cores were higher in the 2.5‐mg/kg risedronate group compared with the OVX group (p< 0.05). BV/TV alone could explain 76% of the variability of the bone strength. The combination of bone volume and architectural variables explained >90% of the strength. The study showed that risedronate preserved trabecular architecture in the vertebra of OVX minipigs, and that bone strength is tightly coupled to bone mass and architecture.

The topical potency of fluticasone propionate (FP) is known to be four times greater than that of triamcinolone acetonide (TAA). However, the significance of this difference has not been proven in the clinical treatment of seasonal allergic rhinitis (SAR).

The U. S. Navy is in the process of modernizing ship structures manufactured before 3‐D computer aided design capabilities were available. Detailed 2‐D views on large engineering drawings can be confusing to personnel performing removal and installation activities. 3‐D tools and capabilities would be highly beneficial to the modernization and implementation of the desired improvements by reducing confusion.

With the proportion of elderly people increasing in many countries, osteoporosis has become a growing public health problem, with rising medical, social, and economic consequences. It is well recognized that a combination of low bone mass and the deterioration of the trabecular architecture underlies osteoporotic fractures. A comprehensive understanding of the relationships between bone mass, the three-dimensional (3D) architecture of bone and bone function is fundamental to the study of new and existing therapies for osteoporosis. Detailed analysis of 3D trabecular architecture, using high-resolution digital imaging techniques such as magnetic resonance microimaging (MRμI), micro-computed tomography (μCT), and direct image analysis, has become feasible only recently. Rapid prototyping technology is used to replicate the complex trabecular architecture on a macroscopic scale for visual or biomechanical analysis. Further, a complete set of 3D image data provides a basis for finite element modeling (FEM) to predict mechanical properties. The goal of this paper is to describe how we can integrate three-dimensional microimaging and image analysis techniques for quantitation of trabecular bone architecture, FEM for virtual biomechanics, and rapid prototyping for enhanced visualization. The integration of these techniques provide us with an unique ability to investigate the role of bone architecture in osteoporotic fractures and to support the development of new therapies. Anat Rec (New Anat) 265:101–110, 2001. © 2001 Wiley-Liss, Inc.

Background:Many patients with persistent asthma need both long-acting bronchodilators and inhaled corticosteroids for optimal asthma control. Objective:Our purpose was to compare the efficacy and safety of salmeterol 50 μg combined with fluticasone 100 μg (in a combination dry powder product) with that of placebo, fluticasone, or salmeterol alone. Methods:A 12-week randomized, double-blind, multicenter study was conducted in 356 patients aged 12 years or older with asthma. After a 14-day screening period, patients were randomized to treatment with salmeterol 50 μg combined with fluticasone 100 μg (combination product), salmeterol 50 μg, fluticasone 100 μg, or placebo administered in the Diskus dry powder inhaler (GlaxoWellcome, UK) twice daily. Results:Mean change in FEV1at end point was significantly (P≤ .003) greater with the combination product (0.51 L) compared with placebo (0.01 L), salmeterol (0.11 L), and flutica-sone (0.28 L). The combination product significantly increased (P≤ .013) area under the curve compared with placebo and fluticasone on day 1 and compared with placebo, salmeterol, and fluticasone at week 1 and week 12. Patients in the combination product group were less likely to withdraw from the study because of worsening asthma compared with those in the other groups (P≤ .020). The combination product significantly increased (P≤ .012) morning PEF (combination, 52.5 L/min; placebo, –23.7 L/min; salmeterol, –1.7 L/min; fluticasone, 17.3 L/min) and evening PEF at end point compared with the other groups. The combination product significantly (P≤ .025) reduced symptom scores and albuterol use compared with the other treatments and increased the percentage of nights with no awakenings and the percentage of days with no symptoms compared with placebo and salmeterol. All treatments were equally well tolerated. Conclusion:Salmeterol 50 μg and fluticasone 100 μg combined in the Diskus powder delivery device offers significant clinical advantages over salmeterol or fluticasone alone at the same doses. (J Allergy Clin Immunol 2000;105:1108-16.)

To compare the dose response, efficacy, and safety of inhaled triamcinolone acetonide (TAA) with a hydrofluoroalkane (HFA) propellant (75 μg/puff), TAA with a chlorofluorocarbon propellant (dichlorodifluoromethane [P-12]; 75μ g/puff), and placebo in adult patients with persistent asthma.

Fluticasone propionate is a topically active glucocorticoid with potent antiinflammatory activity in the treatment of asthma.

The current stepwise approach to pharmacotherapy in the treatment of asthma includes the initiation of an inhaled corticosteroid with the addition of a long-acting inhaled bronchodilator if low dose inhaled corticosteroid fails to control asthma symptoms.

The improved lung deposition of hydrofluoroalkane-134a beclomethasone dipropionate (HFA-BDP) extrafine aerosol compared with chlorofluorocarbon beclomethasone dipropionate (CFC-BDP) suggests that lower doses of HFA-BDP may be required to provide equivalent asthma control. The present study was undertaken to test this hypothesis.

Background:Many clinicians are reluctant to prescribe inhaled corticosteroids because of concerns over potential effects on the hypothalamic-pituitary-adrenal axis. Objective:The purpose of this study was to compare the adrenal responses to 6-hour cosyntropin infusion after treatment with fluticasone propionate aerosol, triamcinolone acetonide aerosol, prednisone, and placebo for 4 weeks, a sufficient time interval to assess any effects on the adrenal response to stress. Methods:This double-blind, triple-dummy, randomized, placebo-controlled study was conducted in 128 patients to evaluate adrenal response to 6-hour cosyntropin infusion (a clinically relevant method for evaluating adrenal function) after 28 days of treatment with fluticasone propionate aerosol 88 μg or 220 μg twice daily, triamcinolone acetonide aerosol 200 μg 4 times daily or 400 μg twice daily, prednisone 10 mg once daily, and placebo. Results:After 28 days of treatment, mean plasma cortisol response to cosyntropin over 12 hours after initiation of the 6-hour infusion was similar among fluticasone, triamcinolone, and placebo groups; cortisol response was significantly (P< .05) reduced after treatment with prednisone compared with the other treatment groups. Mean 8-hour area under the plasma cortisol concentration-time curves and peak plasma cortisol concentrations were significantly (P≤ .003) lower with prednisone than any other treatment; no significant differences were noted between placebo and either of the fluticasone groups in any assessment. Mean reductions from baseline in area under the plasma cortisol concentration time curves and peak cortisol concentrations were significantly (P< .05) greater with triamcinolone 400 μg twice daily compared with placebo. Conclusion:These results suggest that fluticasone propionate at therapeutic doses has effects on the hypothalamic-pituitary-adrenal axis comparable to that of placebo and has significantly less effect than prednisone as measured by 6-hour cosyntropin infusion after 28 days of treatment. (J Allergy Clin Immunol 1999;103:622-8.)

Seasonal allergic rhinitis is a common and distressing illness for which treatment is often inadequate. There is a clinical need for safe and effective therapeutic options, including personal treatment, to manage many of these patients.

Catechol estrogens, estrogen metabolites of potential physiologic significance, were measured in infertile women undergoing ovulation induction with human menopausal gonadotropins.

Twenty-one embolizations were performed in 12 swine using a detachable silicone balloon-catheter system. In 11 embolizations, balloons were filled with 60 meglumine sodium diatrizoate (R-60); 30 meglumine sodium diatrizoate (R-30) was used in 10 embolizations. Serial radiographs were obtained to determine the duration of balloon inflation. Repeat angiography and autopsy examinations were performed three to six months following embolization. Eighty percent of balloons filled with R-30 were still inflated after 10 days, as opposed to 27 of the balloons filled with R-60. Balloons which remained inflated for more than 10 days caused permanent occlusion of the embolized arteries. The vessels were occluded precisely at the point at which the balloons were initially attached. Pathologically, the occluded vessels exhibited organized thrombi with minimal inflammation. Detachable balloons appear to be an effective, safe method of performing selective vascular occlusion in many circulatory systems. Careful control of the volume and osmolarity of the contrast medium used to inflate the balloons produces permanent arterial occlusion.

Abstract: Sonography, computed tomography, and most recently, magnetic resonance imaging (MRI) have been advocated as noninvasive imaging methods for the preoperative evaluation of patients with abdominal aortic aneurysms (AAA). We prospectively assessed the value of MRI in this clinical setying. Twenty of 23 patients with AAA referred for evaluation with biplane aortography underwent MRI within 3 days of aortography. MR and angiographic studies were interpreted prospectively and independently and then the results were compared with each other and with the operative findings. All angiographically demonstrated infrarenal and suprarenal aneurysms except one were documented as such by MRI. The distal extent of the aneurysm on MRI agreed with that on angiography in all but 3 cases. MRI is an accurate method for assessing the size and extent of AAA and its relationship to the main renal artery origins. MRI is not accurate in detecting vascular obstructions or accessory renal arteries. Therefore, the usefulness of MRI and the need for aortography in preoperative assessment of AAA depends upon the specific information the surgeon requires prior to aneurysmectomy in a given patient.

Beginning in July 1988, a planned program was undertaken to assess the role of aortic and pelvic lymphadenectomy in patients with advanced epithelial cancer of the ovary (Stages IIIa-IVa) undergoing cytoreductive surgery. Our intent was to perform a complete aortic and pelvic lymphadenectomy in all patients in whom we could surgically remove all intra- or retroperitoneal disease measuring 1 cm or greater. Accordingly, 56/77 patients (73%) underwent complete aortic and pelvic lymphadenectomy. The remaining 21/77 patients (27%) did not, either because the lymphadenectomy would not have impacted on the patient's cytoreductive status or because intraoperative conditions precluded it. Positive lymph nodes were found in 36/56 patients (64%). Of these, 23/36 (64%) were macroscopically positive, and if left in situ would have affected the patient's cytoreductive status. Thirteen of 36 (36%) were positive microscopically. Reassessment laparotomy was performed in 44/56 (79%) of the patients having had a lymphadenectomy and is correlated to disease status. Median follow-up is 30 months (range 2-64 months). Survival analysis reveals: 10/20 patients (50%) with negative lymph nodes; 6/13 patients (46%) with microscopically positive lymph nodes; 10/23 patients (43%) with macroscopically positive, but surgically removed lymph nodes; and only 2/21 patients (10%) with residual disease measuring at least 1 cm in diameter are alive without evidence of disease. These preliminary findings suggest that the removal of macroscopically negative lymph nodes offers little benefit to the patient with advanced epithelial cancer and minimal residual (less than 1 cm) disease. However, the concept of cytoreductive surgery, whether it be intra- or retroperitoneal, appears to be validated by the fact that the patients undergoing removal of macroscopically positive lymph nodes have approximately the same chance of survival as those with microscopically positive and/or negative lymph nodes. Copyright 1995, 1999 Academic Press

Fluticasone propionate (FP) administered via metered-dose inhaler is a potent corticosteroid effective in the treatment of asthma. To evaluate the efficacy and safety of FP powder administered via a breath-activated inhaler (Diskhaler®), a multicenter, double-blind, randomized, placebo-controlled, parallel-group study was conducted in adolescent and adult patients (n = 331) with mild-to-moderate asthma previously treated with β2-agonist therapy alone. Patients received FP powder 50, 100, or 250 μg or placebo twice daily for 12 weeks. FP-treated patients compared with placebo-treated patients had significantly (p < 0.001) greater improvements in morning predose forced expiratory volume in 1 sec (21-22% increase vs. 9%). Improvement in morning peak flow rate were also significantly (p < 0.001) greater with FP than with placebo (8-10% increase vs. 2% increase). There was also a significant overall treatment difference in the frequency of inhaled albuterol use (p < 0.001) and number of nighttime awakenings due to asthma (p = 0.005). There were no statistically significant differences among the FP treatment groups in any outcome measure. Physicians' global assessments also indicated significant (p < 0.001) differences in efficacy, with 67-74% of FP-treated patients rated as having "effective" or "very effective" treatment compared with 41% of placebo-treated patients. Significant beneficial effects of FP were observed in lung function and diary card parameters after just 1 week of treatment. Adverse events were similar across treatment groups and primarily related to local irritation. Effect on hypothalamic-pituitary-adrenal axis function was minimal. In summary, all three dosages of inhaled FP powder were well tolerated and improved various asthma-related variables. Improvements in pulmonary function, beyond those achieved with β2-agonist therapy alone, were maintained for the duration of the 12-week study.

The role of the spleen in the development of specific antibody-forming cells (sAFC) in the pulmonary draining lymph nodes (pdLNC) of hamsters after local inoculation of sheep erythrocytes (SRBC) was evaluated. The role of the spleen was viewed from two vantage points. Panels of animals were either splenectomized with appropriate sham-operated controls before intratracheal inoculation of SRBC, or panels were immunized intravenously simultaneously with the local inoculation of antigen. The presence of an intact spleen was not necessary for the induction of a sAFC response to occur in the pdLNC. Similar numbers of immunoglobulin M (IgM) sAFC were recorded in the pdLNC on day 4 of both sham-operated and splenectomized animals. However, an enhancement of this local response occurred on day 7 if the animals were systemically immunized and therefore demonstrated active participation of the spleen in the specific immune response. The results support the hypothesis that although a local response may occur in the pdLFC in the absence of a spleen or a splenic response, the presence of a systemic or splenic response appears to be important for the enhancement of local IgM sAFC response. These observations suggest that the immune defenses involved in the lower respiratory tract may differ from those in upper respiratory tract and other mucosally lined organs in that the response of the spleen to the antigen affects the local response to that antigen.

The interdependence of the local and systemic immune systems in the development of the immune responses relating to the lung was evaluated. Hamsters were inoculated with 109sheep erythrocytes (SRBC) via local (intratracheal) or systemic (intravenous) routes of immunization. The local immune response was quantitated by the specific antibody-forming cell (sAFC) response in the pulmonary draining lymph nodes (pdLNC). sAFC in the spleens and serum hemagglutination titers evaluated the systemic immune response. The local inoculation of antigen was superior for induction of the maximal numbers of immunoglobulin M (IgM) and non-IgM sAFC in the pdLNC at 4 days post-immunization. However, the local response coould be enhanced by a concomitant splenic response. The local route of inoculation did not consistently induce an sAFC response in the spleen, but when the spleen was involved, two unique observations were recorded regarding the IgM response: (i) an approximate twofold increase in the numbers of sAFC was seen in the pdLNC on day 7 post-inoculation in animals that had a splenic sAFC response; and (ii) the appearance of an early (day 4) serum IgM hemagglutination titer was observed in the animals with a splenic sAFC response. However, the appearance of IgG serum hemagglutination titers was independent of the indirect sAFC response in the spleen but correlated with the appearance of indirect sAFC response in the pdLNC. As expected, intravenous inoculation of antigen was superior for inducing a systemic IgM response. We concluded that the local and systemic immune responses are related and interdependent in providing immune reactivity related to the lung. Whereas the systemic response enhanced both the serum IgM titer and the specific IgM antibody-forming cell response in the draining nodes, we observed that the local response was sufficient for the IgG serum hemagglutination titer even in the absence of a splenic sAFC response.

The article focuses on the Jeanne A. Carpenter Epilepsy Legal Defense Fund established by the Epilepsy Foundation to help individuals fight unfair practices toward people with epilepsy. It details the legal initiatives launched by the fund on behalf of adults with epilepsy. It cites the efforts of the fund to ensure that children with epilepsy will have full access in schools. It mentions the legal guidance offered by the fund to individuals experiencing discrimination related to epilepsy.

Asthma exacerbation risk increases with worsening asthma control. Prevailing numerical control tools evaluate only current symptom impairment despite the importance of also assessing risk based on exacerbation history. An easy-to-use questionnaire addressing impairment and risk domains of control is needed.

Allergic rhinitis is a prevalent disease, which can be classed as seasonal (SAR) or perennial. In addition to nasal symptoms, up to 75% of sufferers experience itching, redness, and tearing of the eyes. Intranasal corticosteroids are effective in controlling the allergic nasal symptoms, and increasing evidence suggests that they also can relieve some of the allergic ocular symptoms.

GSP301 nasal spray is a fixed-dose combination of olopatadine hydrochloride (antihistamine) and mometasone furoate (corticosteroid).

Chromomycosis is a chronic, slowly progressive disease of the skin and subcutaneous tissue produced by several species of dematiaceous or pigmented fungi, especially Phialophora gougeroti. Verrucous nodules and flattened annular plaques are the most frequently reported skin lesions in chromomycosis, but deep abscesses and cystic lesions have also been reported. We describe herein a case of cystic chromomycosis due to Wangiella dermatitidis that developed following a nonpenetrating injury to the thumb.(Arch Dermatol 115:1433-1434, 1979)

Erythema chronicum migrans with an intensely purpuric border developed in a 70-year-old woman. A biopsy specimen, in addition to showing the usual perivascular mononuclear infiltrate, demonstrated numerous polymorphonuclear leukocytes associated with leukocytoclasis. Immunofluorescence study showed vascular deposition of IgM and C3.(Arch Dermatol 115:873-874, 1979)

Extensive cutaneous lesions that simulated sporotrichosis developed in a patient. Mycobacterium chelonei, a facultative pathogen that exists as a saprophyte in the environment and rarely produces clinical disease in humans, grew from culture of biopsy material. There was no evidence of visceral involvement, and the lesions healed spontaneously within six months.(Arch Dermatol 115:738-739, 1979)

Investigation of fetal red blood cell (RBC) deformability by filtration and viscosimetry has shown that the fetal RBC varies significantly from the adult. Cord blood from 15 newborns was compared with 14 adults. Triple washed RBC's in Eagle's albumin buffer with a hematocrit of 10 ± .5% were passed through a polycarbonate filter with a 3 µ × 13.5 µ cylindrical pore under constant pressure. Flow velocity (µl/sec) was calculated. Cell suspensions were modified by adjusting temperature, pH and pO2 prior to filtration. Mean corpuscular volume (MCV), reticulocyte count and fibrinogen were measured. Viscosity of whole blood, 40% cells in autologous plasma and 80% washed cells was deterined.Filterability, as a measure of RBC deformation, was markedly decreased in newborn samples. Mean flow velocity was 2.2 µl/sec Lowered pH or pO2 in the prefiltrate resulted in significantly decreased filterability in newborn samples only. Filterability correlated poorly with MCV. Two infants with polycythemic hyperviscosity syndrome showed increased viscosity of whole blood, 80% cell suspension and markedly decreased filterability. An infant with pyknocytosis and markedly decreased filterability. An infant with pyknocytosis showed decreased filterability and elevated viscosity of an 80% suspension compared to normal newborns.Decreased deformability of the fetal RBC may be related to shortened newborn RBC survival involving diminished ability to pass through the splenic microcirculation. The decreased fetal RBC deformability which can be aggravated by acidosis and hypoxia contributes to hyperviscosity in newborns with high hematocrits. The decrease in red cell survival and anemia in infantile pyknocytosis may also be related to altered RBC deformability.

Looks at ways to determine whether keeping a customer is for the best interest of a business. Customer problems that may have negative effects on business; Benefits of terminating relations with bad customers.

Alterations in rheologic parameters may play an important role in many disease states. Hyperviscosity secondary to polycythemia, leukocytosis or abnormal blood proteins may contribute to the pathogenesis of serious symptomatology due to sludging of blood flow. Decreased erythrocyte (RBC) deformability may contribute both to hyperviscosity and to the premature removal of sclerocytic erythrocytes by the spleen.In a study of 68 patients during 1970-73 the following rheologic abnormalities were found.(1) Hyperviscosity due to polycythemia in: neonatal hyperviscosity, cyanotic heart disease and cystic fibrosis.(2) Decreased RBC deformability alone in: respiratory distress syndrome, infants of diabetic mothers, immune hemolysis, infantile pyknocytosis, advanced liver disease, nephrosls, renal failure and intrinsic RBC defects.(3) Hyperviscosity of whole blood due to both polycythemia and decreased RBC deformability in: neonatal hyperviscosity syndrome, infants of diabetic mothers and cystic fibrosis.(4) Hyperviscosity due to increased leukocytes in: the myeloproliferative syndrome of trisomy 21 and acute leukemia.(5) Hyperviscosity due to parenteral protein concentrates in: hemophilia after intensive transfusion.Investigation into the role of altered rheology in these conditions may increase our knowledge of disease mechanisms and associated laboratory and clinical findings.