Modifications of granulocyte subpopulations and of their adherence property during filtration leukapheresis in man

S ummary . Polymorphonuclear leucocytes (PMN) isolated from the peripheral blood of 23 blood donors undergoing filtration leukapheresis were examined with regard to their number, expression of membrane receptors for rabbit IgG or human C3b and their ability to adhere to nylon fibres. All the donors showed an early granulocytopenia followed by a gradual return of PMN into the circulation, but differed in the number of PMN appearing in the rebound phase. Evaluation of rosette forming cells (RFC) and cells adhering to nylon fibres in this phase led to the recognition of two main groups of donors. In one of these groups the number of PMN, RFC and adhering cells remained unchanged compared to the pre-apheresis values. The other group showed marked leucocytosis accompanied by a relative increase in the number of non-RFC and non-adhering cells. Possible mechanisms involved in the changes of PMN subpopulations are discussed.     

Assessment of allergy to local anesthetic

A 57-year-old woman with a history of allergy to local anesthetics was referred to us to be admitted for a general anesthetic for removal of a sliver from her finger. Because allergic reaction to local anesthetics often is caused by an anesthetic other than lidocaine, or is due to the carrier vehicle in the diluent, a skin test with pure lidocaine was performed. After showing no reaction, the patient was given the standard dose of lidocaine and the sliver was removed in the emergency department. The patient was discharged home with no sequelae.     

The effect of anti-inflammatory agents and inflammation on granulocyte adherence: Evidence for regulation by plasma factors

Significant inhibition of granulocyte adherence to nylon fiber columns followed the administration of alcohol, aspirin, sodium salicylate, acetaminophen, indomethacin, phenylbutazone, colchicine or prednisone to normal subjects. The addition of salicylates and glucocorticoids to blood in vitro had no effect on adherence, but plasma from volunteer subjects treated with either drug contained a factor which inhibited the adherence of normal granulocytes. The factor is heat stable, nondialyzable and not present in serum; it produces a linear dose response in normal cells. When mixed with the adherence-increasing factor found in inflammatory diseases, it neutralizes the augmenting effect and normal granulocyte adherence results.The effect of anti-inflammatory therapy on inflammatory disease was studied in aspirin-treated patients with rheumatoid arthritis. Their granulocyte adherence fell into two categories based on the clinical control of their disease: patients in good control had only slightly increased granulocyte adherence, but those in poor control had an average adherence more than twice normal. Mean blood aspirin levels were equivalent for the two groups ($\text{11.0}\text{mg}\text{100}\text{ml}$ for the well controlled and $\text{13.4}\text{mg}\text{100}\text{ml}$ for those poorly controlled). Thus, clinical response to anti-inflammatory therapy correlates well with granulocyte adherence, not with aspirin levels. The potential pathogenetic role of adherence-modifying factors in inflammatory diseases remains to be determined.     

Salicylate blockade of granulocyte adherence and the inflammatory response to experimental peritonitis.

Aspirin profoundly inhibited the in vitro augmentation of human and mouse granulocyte adherence to nylon fiber induced by the bacterial products Escherichia coli endotoxin and Staphylococcus aureus culture filtrate. Granulocytes obtained from normal volunteers during the 48 hr following ingestion of aspirin did not respond normally to endotoxin stimulation. Furthermore, pretreatment of mice with sodium salicylate prior to intraperitoneal infection with Streptococcus pneumoniae impaired granulocyte exudation and resulted in uncontrolled bacteremia and greater lethality of infection.     

Real-world experience of treating frozen shoulder using active manipulation under local anesthetic: A retrospective study

Currently, there is limited evidence to guide treatment and no standard management guidelines exist for treating frozen shoulder (FS). A general management approach consists of initial evaluation, range of motion (ROM) exercises, intra-articular injection of glucocorticoid, home exercise program (HEP), and/or physical therapies. However, the general approach lacks detail and has limited evidence of its effectiveness. This retrospective cohort study evaluates the short-term recovery of near-full to full-ROM technique followed by an instructed HEP for strengthening and coordinating shoulder girdle muscle group for FS management. This study details our experiences following a general approach to managing FS and aims to fill this knowledge void, providing additional context of the efficacy of FS management in the real-world. Seven-two adult patients with FS (46 females, 26 males; mean age of 66; standard deviation of 15.1; range 23–87) from an orthopedic and physical medicine and sport medicine office between 2014 and 2018 were included in this study. Following general management of FS, patients received a glucocorticoid–lidocaine mixture injection administered to the respective shoulder at the glenohumeral joint space and/or subacromial separately. Immediately, patients underwent active manipulation of the affected shoulder in 3 directions: forward flexion, abduction, and extension in the sagittal plane. Lastly, patients were instructed to perform movements similar to the active manipulation protocol as a HEP. The abduction and forward flexion ROM showed significant improvements with the described protocol. Following treatment, there was a 90.20° and 77.33° increase in average shoulder abduction and forward flexion ROM, respectively (P < .05). The immediate goal of this protocol was to gain maximum ROM in different directions of shoulder mobility. Following the general management of FS, active manipulation under local anesthetic was a highly effective treatment modality for adhesive capsulitis that was time-saving and cost-effective.     

利多卡因局部麻醉用于清醒支气管镜检查的效果和安全性研究

目的 调查和评价利多卡因局部麻醉在清醒支气管镜检查的效果和安全性,为医护人员合理使用利多卡因局部麻醉提供依据.方法 选择在山东大学齐鲁医院接受首次支气管镜检查的115例清醒的住院患者为研究对象,检查前用利多卡因喉头喷雾麻醉,检查后统计患者呛咳发生率、利多卡因使用量和不良反应.气管镜检查结束5 min之内静脉采血,检测患者的血药浓度,并采用半结构式访谈法了解患者对利多卡因局部麻醉的接受程度.结果 呛咳发生率：会厌7.8％,声门17.3％,隆突上37.4％,左右主支气管39.1％,叶支气管97.4％,喉头喷雾麻醉后,会厌、声门的呛咳发生率明显低于气管及各级支气管的呛咳率（P＜0.05）;每例患者利多卡因平均使用（19.7±5.2） ml（14～25 ml）,使用10～＜15 ml占总人数的2.6％,15～＜20 ml占67.0％,20～25 ml占30.4％,使用15～＜20 ml利多卡因的患者明显多于其余2个范围的患者（P＜0.05）;利多卡因平均血药浓度（2.0±1.1） mg/L（0.5～3.6 mg/L）,均低于5 mg/L;98.3％的患者可接受利多卡因局部麻醉;主要不良反应包括血压升高30.4％,头晕、恶心6.1％,心动过缓2.6％,呼吸困难1.7％,心衰0.9％,总发生率为41.7％.结论 利多卡因局部麻醉用于清醒支气管镜检查效果可靠,认可度高且安全,适合作为支气管镜检查的麻醉方式.     

Antiviral agents targeted to interact with viral capsid proteins and a possible application to human immunodeficiency virus

The tertiary structure of most icosahedral viral capsid proteins consists of an eight-stranded antiparallel beta-barrel with a hydrophobic interior. In a group of picornaviruses, this hydrophobic pocket can be filled by suitable organic molecules, which thereby stop viral uncoating after attachment and penetration into the host cell. The antiviral activity of these agents is probably due to increased rigidity of the capsid protein, which inhibits disassembly. The hydrophobic pocket may be an essential functional component of the protein and, therefore, may have been conserved in the evolution of many viruses from a common precursor. Since eight-stranded anti-parallel beta-barrels, with a topology as in viral capsid proteins, are not generally found for other proteins involved in cell metabolism, this class of antiviral agents is likely to be more virus-specific and less cytotoxic. Furthermore, the greatest conservation of viral capsid proteins occurs within this pocket, whereas the least conserved part is the antigenic exterior. Thus, compounds that bind to such a pocket are likely to be effective against a broader group of serologically distinct viruses. Discovery of antiviral agents of this type will, therefore, depend on designing compounds that can enter and fit snugly into the hydrophobic pocket of a particular viral capsid protein. The major capsid protein, p24, of human immunodeficiency virus would be a likely suitable target.     

Choices, persistence and adherence to antihypertensive agents: evidence from RAMQ data

BACKGROUND:

Most treatment recommendations for hypertension are based on criteria that consider efficacy, safety and cost. Given the need for long-term use of antihypertensive agents, treatment compliance should also be taken into consideration in the selection process.

OBJECTIVE:

The purpose of the present study was to estimate persistence and adherence to antihypertensive agents in a real-life setting.

METHODS:

Persistence and adherence to treatment were estimated using data from the Regie de l’assurance maladie du Quebec.

RESULTS:

Data from a random sample of 4561 subjects with a diagnosis of hypertension covered by the Regie de l’assurance maladie du Quebec drug plan and using one of the antihypertensive agents reimbursed by the drug plan for the first time between January 2000 and December 2001 were analyzed. The persistence rate observed after a two-year period with diuretics was significantly lower (52.8%) than with any other classes of antihyperten-sive agent (P<0.01). Persistence rates for beta-blockers, calcium channel blockers, angiotensin-II receptor blockers and angiotensin-I converting enzyme inhibitors were 69.3%, 64.3%, 60.9% and 58.9%, respectively. After two years, the proportion of patients who were 80% adherent to their treatment was 64.9% for angiotensin-I converting enzyme inhibitors, 65.0% for angiotensin-II receptor blockers, 64.2% for calcium channel blockers, 60.3% for beta-blockers and 50.9% for diuretics. The proportion of patients who were 80% adherent to their treatment was significantly lower for diuretics than with any other antihypertensive agents (P<0.01).

CONCLUSION:

Persistence and adherence to treatment are essential to treatment success. Results of the present study indicate that, in a real-life setting, patients are significantly less compliant to diuretics than to any other antihypertensive agents.     

Collagenous colitis: possible response to sulfasalazine and local steroid therapy

A patient with rheumatoid arthritis and collagenous colitis apparently responding to sulfasalazine and prednisolone enemas is reported. It is suggested that this form of therapy should be considered in patients with this rare disorder not only as a short-term measure but also, in the case of sulfasalazine, as long-term treatment in patients with chronic symptoms.     

Better adherence to antihypertensive agents and risk reduction of chronic heart failure

Aims. Antihypertensive (AH) agents have been shown to reduce the risk of major cardiovascular events including chronic heart failure (CHF). However, the impact of changes in patterns of AH agents use on CHF is unknown. Our objective was to estimate to which different patterns of AH agent use is associated with the occurrence of CHF in a population‐based study. Method and results. A cohort of 82 320 patients was reconstructed using the Régie de l’assurance maladie du Québec’s databases. Patients were eligible if they were between 45 to 85 years of age, had no indication of cardiovascular disease and were newly treated with AH therapy between 1999 and 2004. A nested case–control design was used to study the occurrence of CHF. Every case of CHF was matched for age and duration of follow‐up to a maximum of 15 randomly selected controls. Adherence level was reported as a medication possession ratio. Conditional logistic regression models were used to estimate the rate ratio (RR) of CHF adjusting for different covariables. The mean patient age was 65 years, 37% were male, 8% had diabetes, 19% had dyslipidaemia and mean time of follow‐up at 2.7 years. High adherence level (95%) to AH therapy compared with lower adherence level (60%) was associated with an additional reduction of CHF events (RR: 0.89; 0.80–0.99). Risk factors for CHF were being on social assistance, diabetes, dyslipidaemia, higher chronic disease score and developing a cardiovascular condition during follow‐up. Conclusion. Our study suggests that a better adherence is associated with a significant risk reduction of CHF. Adherence to AH therapy needs to be improved to optimize benefits.     

Factors that influence adherence to exercise and their effectiveness: application to cystic fibrosis

Appropriate, regular exercise is of benefit to patients with cystic fibrosis (CF). As with other segments of the population, it has been difficult to devise exercise programs to which most patients will adhere for long periods of time. In healthy children, factors that are related to positive exercise compliance include social support, perceptions of competency and self-esteem, enjoyment of activity, and availability of a variety of activities. In patients with CF, complications associated with the disease, e.g., time required for other treatment and fatigue, make compliance with recommended exercise activities more difficult. Factors likely to increase compliance in this population include explicit and continued encouragement and support from the family and healthcare team, and the introduction of behavior-changing strategies.     

Adverse reactions during transfusion of thawed haematopoietic progenitor cells from apheresis are closely related to the number of granulocyte cells in the leukapheresis product

Background and Objectives The infusion of thawed haematopoietic progenitor cells from apheresis (HPC‐A) is associated with minor but frequent adverse reactions (ARs), which has been mainly attributed to dimethyl sulphoxide (DMSO). Nevertheless, other factors may play a role in the pathogenesis of such toxicity. Materials and Methods The ARs on a cohort of 423 cryopreserved HPC‐A infusions for 398 patients in HPC transplantation program were analysed. Results ARs were reported in 105 graft infusions (24·8%) and most of them were graded as mild to moderate. The most frequently reported ARs were gastrointestinal and respiratory, and three patients presented epileptic seizure. The volume of DMSO/kg (P < 0·001), volume of red‐blood‐cells/kg (P = 0·02), number of nuclear cells (NCs)/kg (P < 0·001) and number of granulocytes/kg (P < 0·001) in the infused graft were significant in the univariate analysis for the occurrence of ARs. The amount of granulocytes/kg remained significant in the multivariate analysis (P < 0·001). The grade of ARs also correlated with the amount of cryopreserved granulocytes. Conclusion The incidence and grade of ARs during infusion of cryopreserved HPC‐A are related to the amount of granulocytes in the graft.     

Buffered lidocaine as a local anesthetic: an investigation of shelf life.

STUDY OBJECTIVE: To determine whether buffered lidocaine must be prepared just before use. DESIGN: Randomized, double-blind, prospective trial. SETTING: University hospital. PARTICIPANTS: Twenty-four adult volunteers. INTERVENTIONS: Three buffered lidocaine solutions prepared seven days, one day, and just before use were compared with a control solution. Subjects received 0.5 mL intradermal injections of each solution. Pain of infiltration and extent and duration of anesthesia were measured. MEASUREMENTS AND MAIN RESULTS: Pain of infiltration was less with all buffered solutions than control (P less than .0001). Mean maximum diameter of anesthesia ranged from 29 to 33 mm for the buffered solutions compared with 31 mm for control. Mean duration of anesthesia was 33 minutes for control and 30 minutes for all of the buffered solutions. There was no statistically significant difference in extent or duration of anesthesia for any of the solutions (P greater than .5, beta = .15 for delta = 10%). CONCLUSION: Buffered lidocaine stays effective for up to one week after preparation. It is therefore convenient to use in emergency settings.