Chemical imaging of a Symbiodinium sp. cell using synchrotron infrared microspectroscopy: a feasibility study.

The symbiotic relationship between corals and Symbiodinium spp. is the key to the success and survival of coral reef ecosystems the world over. Nutrient exchange and chemical communication between the two partners provides the foundation of this key relationship, yet we are far from a complete understanding of these processes. This is due, in part, to the difficulties associated with studying an intracellular symbiosis at the small spatial scales required to elucidate metabolic interactions between the two partners. This feasibility study, which accompanied a more extensive investigation of fixed Symbiodinium cells (data unpublished), examines the potential of using synchrotron radiation infrared microspectroscopy (SR-IRM) for exploring metabolite localisation within a single Symbiodinium cell. In doing so, three chemically distinct subcellular regions of a single Symbiodinium cell were established and correlated to cellular function based on assignment of diagnostic chemical classes.

Associations of physical activity with anxiety symptoms and status: results from The Irish longitudinal study on ageing.

AIMS: Anxiety is debilitating and associated with numerous mental and physical comorbidities. There is a need to identify and investigate low-risk prevention and treatment strategies. Therefore, the purpose of this study was to investigate cross-sectional and longitudinal associations between different volumes of moderate-to-vigorous physical activity (PA) and anxiety symptoms and status among older adults in Ireland. METHODS: Participants (n = 4175; 56.8% female) aged ⩾50 years completed the International PA Questionnaire (IPAQ) at baseline, and the anxiety subscale of the Hospital Anxiety and Depression Scale at baseline and follow-up (2009-2013). Participants were classified according to meeting World Health Organisation PA guidelines, and divided into IPAQ categories. Respondents without anxiety at baseline (n = 3165) were included in prospective analyses. Data were analysed in 2017. RESULTS: Anxiety symptoms were significantly higher among females than males (p < 0.001). Models were adjusted for age, sex, waist circumference, social class, smoking status and pain. In cross-sectional analyses, meeting PA guidelines was associated with 9.3% (OR = 0.91, 95% confidence interval 0.78-1.06) lower odds of anxiety. Compared with the inactive group, the minimally- and very-active groups were associated with 8.4% (OR = 0.92, 0.76-1.10) and 18.8% (OR = 0.81, 0.67-0.98) lower odds of anxiety, respectively. In prospective analyses, meeting guidelines was associated with 6.3% (OR = 0.94, 0.63-1.40) reduced odds of anxiety. Compared with the inactive group, the minimally and very-active groups were associated with 43.5% (OR = 1.44, 0.89-2.32) increased, and 4.3% (OR = 0.96, 0.56-1.63) reduced odds of anxiety. The presence of pain, included in models as a covariate, was associated with a 108.7% (OR = 2.09, 1.80-2.42) increase in odds of prevalent anxiety, and a 109.7% (OR = 2.10, 1.41-3.11) increase in odds of incident anxiety. CONCLUSION: High volumes of PA are cross-sectionally associated with lower anxiety symptoms and status, with a potential dose-response apparent. However, significant associations were not observed in prospective analyses. The low absolute number of incident anxiety cases (n = 109) potentially influenced these findings. Further, as older adults may tend to experience and/or report more somatic anxiety symptoms, and the HADS focuses primarily on cognitive symptoms, it is plausible that the HADS was not an optimal measure of anxiety symptoms in the current population.

Physical activity correlates among older adults with probable generalized anxiety disorder: Results from The Irish Longitudinal Study on Ageing.

OBJECTIVES: This study assessed physical activity (PA) correlates among 1237 (69.0% female; age ≥ 50 years) community-dwelling adults with probable-generalized anxiety disorder (GAD). METHODS: Wave 1 data from The Irish Longitudinal Study on Ageing were analysed. PA was measured using the short-form International PA Questionnaire. Probable-GAD caseness was indicated by a score of ≥23 on the abbreviated Penn State Worry Questionnaire. Potential correlates were analysed using binomial logistic regression. Hierarchical logistic regression consisting of three blocks (sociodemographic variables; quality of life (QoL) variables; physical health and performance variables) examined the proportion of the variance for PA that was explained at each step of the regression model. RESULTS: Five hundred thirty-five participants (43.2%) met PA guidelines. After adjustment for age and sex, younger age and being male were associated with increased likelihood of meeting PA guidelines. Significant correlates of PA were in employment, higher QoL (CASP-19), social connectedness, and grip-strength. Additionally, polypharmacy (i.e., taking ≥five medications), antidepressant use, at-risk waist circumference (i.e., Males: >94 cm; Females >80 cm), up-and-go time, and number of self-reported physical limitations were significantly negatively associated with meeting PA guidelines. Physical health and performance variables explained significant variation (8.4%) in meeting physical activity guidelines beyond that of sociodemographics, and QoL variables. CONCLUSIONS: This study identified a range of sociodemographic, physical, and psychological variables that were associated with meeting or not meeting PA guidelines among older adults with probable-GAD.

Protein A-independent tumoricidal responses in dogs after extracorporeal perfusion of plasma over Staphylococcus aureus.

Protein A-positive or -negative Staphylococcus aureus preparations were used in an extracorporeal system to treat dogs with spontaneously occurring cancers. Tumor regression was seen in 4 of 7 dogs treated by reinfusion of plasma that had been incubated with protein A-positive S. aureus Cowan I strain (SAC). Therapy was associated with fever, liver enzyme abnormalities, and hypocomplementemia. Tumor response and toxicity could be diminished by more extensive washing of the SAC preparation. Tumor regression was also seen in 2 of 2 animals treated with protein A-negative S. aureus Wood strain 46. In addition, tumors regressed in 3 of 4 dogs treated with infusions of protein A-free saline extracts from S. aureus. These results suggest that the release of a non-protein A bacterial product contributes to tumor regression following incubation of plasma with S. aureus.

Circulating immune complexes in sera of dogs with benign and malignant breast disease.

The Raji cell radioimmunoassay was adapted to measure circulating immune complexes (CIC's) in the sera of 74 dogs with benign and malignant breast disease. In dogs with recently diagnosed spontaneous breast cancer, 57% (29 of 51) had elevated CIC's, with some levels as high as those found in the sera of dogs with systemic lupus erythematosus. The sera of 10 of 23 dogs with benign breast disease also demonstrated elevated levels of CIC's. Two weeks following mastectomy, repeat CIC levels were obtained in 30 dogs. Elevated CIC levels returned to normal in all dogs with benign breast disease but in only 33% of dogs with breast cancer. Dogs with persistent elevation of CIC's were at greater risk of developing metastatic breast cancer. Serum total hemolytic complement was significantly higher (p < 0.05) in dogs with untreated breast cancer than in healthy dogs but did not correlate with the level of CIC's found. Two weeks after mastectomy, total hemolytic complement levels had returned to normal. By sucrose density gradient ultracentrifugation, the complexes were shown to sediment at 19 S. These studies indicate that the dog may be a good model for elucidating the significance of elevated CIC's in breast cancer.

Extracorporeal LDL cholesterol removal: role of LDL-pheresis in combination with other hypolipidemic therapy to regress vascular disease.

The direct relationship between hypercholesterolemia and atherosclerosis has resulted in formal cholesterol-lowering recommendations for patients at increased risk. The incomplete response to therapy of some forms of hypercholesterolemia as well as not uncommon drug intolerance prompted the development of extracorporeal techniques to reduce serum cholesterol levels. Nonhuman primate data and an analysis of human cholesterol epidemiology and reduction trials were used to establish guidelines that would maximize the likelihood of stabilizing or regressing established coronary artery atherosclerosis. These goals are a total cholesterol (TC) level of less than or equal to 150 mg/dL (3.9 mmol/L) and a ratio of TC to high-density lipoprotein cholesterol (HDL) of less than 2.8. Selective, extracorporeal removal of LDL cholesterol (LDL-pheresis) was combined with diet and hypolipidemic drugs in a pilot study at The Rogosin Institute to achieve these lipid end-points. Technical aspects of LDL-pheresis, the background rationale for its use as part of a combined hypolipidemic therapy, the initial experience at The Rogosin Institute, and plans for future studies and applications are presented.

Removal of low-density lipoproteins in patients by extracorporeal immunoadsorption.

A new technique called LDL-pheresis was used in patients to lower low-density lipoprotein cholesterol levels. This procedure combines continuous extracorporeal plasma separation with immunoadsorption of low-density lipoprotein on columns containing monospecific antibody to human apolipoprotein B. Six patients underwent a total of 164 procedures without significant side effects or nonspecific protein depletion. Acutely, LDL-pheresis lowered plasma cholesterol levels by removing up to 82 percent of the circulating low-density lipoprotein. Weekly LDL-pheresis combined with a portacaval shunt in a patient with homozygous familial hypercholesterolemia resulted in normalization of plasma cholesterol levels and rapid regression of skin xanthomata. Three of four patients with atherosclerotic coronary artery disease have noted improvement in their angina. LDL-pheresis appears to be a promising new technique capable of safely and efficiently lowering plasma low-density lipoprotein cholesterol levels.

Indications for low-density lipoprotein apheresis.

Low-density lipoprotein (LDL) apheresis offers an additional approach to lipid lowering in patients with severe hypercholesterolemia who fail to respond adequately to diet and drug therapy. Well-defined criteria for patient selection have yet to be established for LDL apheresis. This study proposes guidelines based on whether coronary artery disease (CAD) is present and on the degree of LDL cholesterol elevation after treatment with diet and maximal drug therapy. It is reasonable to consider LDL apheresis therapy for: (1) patients with CAD and LDL cholesterol levels > 190 mg/dl; (2) patients without CAD, but at high risk for disease due to an LDL cholesterol level > 250 mg/dl, a first-degree relative with premature CAD, and the presence of > or = 1 additional risk factor. In addition, LDL apheresis is recommended for the management of all patients with homozygous familial hypercholesterolemia due to the very high risk of CAD and the poor response to usual lipid-lowering treatments.

Treatment of refractory familial hypercholesterolemia by low-density lipoprotein apheresis using an automated dextran sulfate cellulose adsorption system. The Liposorber Study Group.

A subgroup of patients with familial hypercholesterolemia (FH) respond inadequately to standard diet and drug therapy, and are therefore at high risk for the premature development or progression of coronary artery disease. This study evaluated low-density lipoprotein (LDL) cholesterol and lipoprotein (a) removal in a multicenter, controlled trial with a new LDL apheresis procedure (Liposorber LA-15 System). The study comprised patients with FH who had not responded adequately to diet and maximal drug therapy. There were 54 patients with heterozygous FH (45 randomized to treatment and 9 control subjects) and 10 with homozygous FH (all of whom received LDL apheresis). The study included three 6-week treatment phases and a 4-week rebound phase. Treatments were administered at 7- to 14-day intervals. Mean acute reductions in LDL cholesterol were 76% in heterozygous FH patients and 81% in homozygous ones. Time-averaged levels of LDL cholesterol were reduced 41% (243 to 143 mg/dl) in heterozygous FH patients and 53% (447 to 210 mg/dl) in homozygous ones. The substantial acute reduction of lipoprotein (a) (means: 65%, heterozygous FH; 68%, homozygous FH) has not been reported with other therapies. The Liposorber LA-15 System represents an important therapeutic option in FH patients who respond inadequately to diet and drug therapy.

Long-term effects of low-density lipoprotein apheresis using an automated dextran sulfate cellulose adsorption system. Liposorber Study Group.

The short-term effectiveness of low-density lipoprotein (LDL) apheresis using a dextran sulfate cellulose adsorption column technique was previously examined in a 9-center, 22-week controlled trial in 64 patients with familial hypercholesterolemia (FH) who did not adequately respond to diet and drug therapy. Forty-nine patients (40 treatment, 9 controls) subsequently received LDL apheresis procedures as part of an optional follow-up phase. This study reports on the long-term safety, lipid lowering, and clinical efficacy of LDL apheresis for the 5-year period that includes both the initial controlled study and follow-up phase. During this time, patients received a total of 3,902 treatments of which 3,314 treatments were given during the follow-up phase. Adverse events were infrequent, occurring in 142 procedures (3.6%). Immediate reduction in LDL cholesterol was 76% both in homozygotes and in heterozygotes. Patients with homozygous FH had a progressive decrease in pretreatment LDL cholesterol level along with an increase in high-density lipoprotein (HDL) cholesterol level. There was no appreciable change in pretreatment lipoprotein level over time in heterozygotes. The rate of cardiovascular events during therapy with LDL apheresis and lipid-lowering drugs was 3.5 events per 1,000 patient-months of treatment compared with 6.3 events per 1,000 patient-months for the 5 years before LDL apheresis therapy. These findings support the long-term safety and clinical efficacy of LDL apheresis in patients with heterozygous and homozygous FH who are inadequately controlled with drug therapy.

Immunotherapy: rationale and mechanisms.

Immunotherapy is defined as the controlled exposure to known allergens to reduce the severity of the allergic response. Although available since 1910, its exact mechanisms of action is not known but may involve an increase in allergen-specific IgG antibodies, a decrease in IgE synthesis, and alteration in T-lymphocyte activity. Immunotherapy is indicated in patients with proven allergy who have significant symptoms. It may be used together with pharmacologic measures but is relatively contraindicated in patients receiving beta-blocker therapy. Immunotherapy may be continued during pregnancy and should not be initiated in patients with autoimmune diseases or in human immunodeficiency virus-positive patients. Selection of appropriate diagnostic tests is important. Before immunotherapy is considered, there are two recommended in vivo tests (combined prick and intradermal skin test, and skin end point titration) and two recommended in vitro tests (radioallergosorbent test [RAST] and enzyme-linked immunosorbent assays [ELISA]), all equally safe and sensitive. After appropriate test interpretation, treatment is initiated with slowly escalating doses of allergen. Effects are often apparent in 3 to 6 months and, after continuation for 3 to 5 years, patients usually achieve lasting benefit.

Future immunotherapy: what lies ahead?

There is currently great interest in developing improved methods of immunotherapy and new techniques of immune system manipulation to ameliorate allergic diseases. This article reviews current research trends in the immunologic treatment of allergy, including the use of chemically modified allergens, nonparenteral allergen exposure, sustained-release allergen delivery, anti-immunoglobulin E antibodies, gamma-globulin, immune complexes, cytokines, and T-cell-tolerogenic peptides.

Immunotherapy basics.

Immunotherapy is the use of controlled exposure to allergens to produce durable antiinflammatory effects, thus reducing the severity of allergic disorders. Immunotherapy is useful when other methods of allergy therapy are not fully satisfactory and can be effectively combined with rhinologic surgical treatment. Immunotherapy should always be considered as a treatment option for allergy patients and can often be of benefit, provided that appropriate indications and contraindications are observed. Physicians caring for patients with allergies should therefore become familiar with methods of allergy and diagnosis and with the therapeutic potential of immunotherapy. The history of immunotherapy, possible mechanisms, indications, contraindications, testing methods, and initiation of treatment are reviewed.

Subclavian vein thrombosis associated with central venous cannulation in head and neck surgery.

This study reports our experience with eight cases of subclavian vein thrombosis in patients with head and neck cancer. The extent of patients' underlying disease, surgical procedures or radiotherapy performed, relationship to central venous catheters, nature of the thrombosis, incidence of emboli, and therapy instituted are examined. Analysis of these cases reveals that 43% (three patients) developed pulmonary emboli despite therapy. Stage IV disease was present in 86% (seven) of the patients in this review. Specific recommendations regarding early recognition, diagnosis, treatment, and possible implications for head and neck surgical procedures are made.

Safety of home-based and office allergy immunotherapy: A multicenter prospective study.

During a 1-year period, 27 otolaryngic allergy practices recorded all systemic reactions to immunotherapy resulting from 635,600 patient visits and 1,144,000 injections. Sixty percent of injections were given at home. Major systemic reactions were observed after 0. 005% of injections. There were no hospitalizations or deaths. Eighty-seven percent of major reactions began within 20 minutes of injection. Frequently observed risk factors for major reactions were buildup phase of immunotherapy, active asthma, and first injection from a treatment vial. Home and office injections had similar rates of total systemic reactions, but home-based immunotherapy had far fewer major reactions. Home-based immunotherapy was found to be safe. The methods and precautions used to treat patients with this degree of safety are specified and discussed.

Prevention and management of office allergy emergencies.

Acute anaphylaxis is a rare, potentially fatal, multisystem allergic reaction that every allergy office must be prepared to treat. Key points are reaction prevention, diagnosing the serious reaction, proper staff training, and keeping on hand (readily accessible and in functioning condition) adequate supplies to provide emergency treatment appropriate to the office locale. The diagnosis of, and treatment for, each common type of allergic reaction is discussed. Equipment and medicines suggested for office use are reviewed, and a sample allergy reaction management protocol is outlined. Office treatment of anaphylaxis is directed at stabilizing the patient for early transport to a hospital. Early administration of epinephrine is the most crucial step. The airway is maintained, circulation supported, and further mediator effects blocked. Cardiopulmonary resuscitation is used whenever respiration or circulation is insufficient. Stabilized patients should be transported as soon as possible by the most medically capable method available, preferably by ambulance with medical personnel in attendance. Because of the risk of subsequent delayed onset or late-phase reactions, and the possibility of multiorgan injury, anaphylaxis patients should be considered for admission to the hospital, extended observation, and appropriate specialist consultations.

Allergy skin tests for inhalants and foods. Comparison of methods in common use.

Many types of skin tests have evolved from Blackley's early scratch tests. This review highlights both the similarities between current skin tests and their differences. All current skin tests are capable of detecting allergic hypersensitivity, but the tests differ in their sensitivity, specificity, safety, reproducibility, and applications. Common factors in initial and final test doses, and in test dose increments, are identified. Test methods that quantitatively measure a range of allergen concentrations have diagnostic advantages in terms of safely detecting a wide range of allergic sensitivities. Failure to detect the full spectrum of allergic disease can lead to treatment failure; therefore, complete skin testing is desirable. This is especially important when dealing with exquisitely sensitive patients, such as many grass or ragweed sensitized patients, but is equally vital when evaluating low sensitivity patients, including many who are mold or food sensitive. Quantitation also improves test reproducibility, which is why it is used for antigen standardization. Finally, quantitation has advantages when used to initiate and escalate allergen immunotherapy. In vivo testing continues to evolve. New types of prick testing devices, and refinements of intradermal and patch test methods, continue to be reported. All allergists need to stay current with developments in vivo testing, so that they can offer their patients diagnosis that is appropriate to each individual situation.

Plasmapheresis-immunoadsorption for treatment of systemic lupus erythematosus in a dog.

Systemic lupus erythematosus was diagnosed in a 3-year-old, male German Shepherd Dog. Clinical signs included lethargy, partial anorexia, fever, joint swelling, and skin and oral ulceration. The diagnosis was confirmed on the basis of an antinuclear antibody titer of 1:640 and immunofluorescence for immunoglobulin G at the dermal-epidermal junction in skin biopsy specimens. Treatment with prednisone and cyclophosphamide failed to induce remission. Intensive plasmapheresis-immunoadsorption, using purified Staphylococcus protein A in combination with low-dose prednisone therapy, resulted in sustained remission.

Plasmapheresis and chemotherapy of hyperviscosity syndrome associated with monoclonal gammopathy in the dog.

Hyperviscosity syndrome associated with IgA monoclonal gammopathy was diagnosed in 3 dogs. Continuous plasmapheresis and alkylation therapy with melphalan and cyclophosphamide induced sustained remission in each dog. There was resolution of clinical signs associated with hyperviscosity syndrome and rapid establishment of normal serum protein concentrations.

Plasmapheresis as adjuvant therapy for autoimmune hemolytic anemia in two dogs.

Severe, acute, autoimmune hemolytic anemia in 2 dogs was treated, using prednisone, cyclophosphamide, plasmapheresis, and blood transfusion. In 1 case, splenectomy was performed successfully after plasmapheresis and blood transfusion. Antibody removal by means of plasmapheresis effected short-term stabilization to severe hemolysis in both dogs, but was suspected to have contributed to the death of 1 dog.