Expression of specific granule markers on the cell surface of neutrophil cytoplasts

The widespread assumption that cytoplasts generated from human polymorphonuclear leukocytes (PMNs) are vesicles consisting solely of cytoplasm surrounded by plasma membrane and devoid of granule activity remains to be tested. PMN cytoplasts were prepared by centrifugation of intact cells on a Ficoll step gradient in the presence of cytochalasin B. Two granule membrane markers, Mol, a fluorometrically detectable antigen, and cytochrome b, both of which have been shown to translocate to the plasma membrane during granule release, were compared for their activity in cytoplasts and intact PMNs. We found that the amount of Mol detected on the plasma membrane of intact PMNs, as compared with other membrane markers (such as antigens LFA-1 and beta 2m), increased 1.6- fold upon exposure of PMNs to Ficoll plus cytochalasin B prior to centrifugation. Another twofold increase in Mol expression occurred upon cytoplast preparation. Release of the granule enzymes, vitamin B12- binding protein, and lysozyme were also followed and correlated well (r = .78 and .92) with the amount of Mol antigen present on the cell surface. Cytochrome b was also found to be higher (1.4-fold) on plasma membranes isolated from cytoplasts than on plasma membranes isolated from intact control cells. These results indicate that some fusion of granule membranes and plasma membranes occurred during treatment of PMNs with Ficoll plus cytochalasin b and during cytoplast preparation.     

Double-blind crossover randomized trial of intravenously administered verapamil. Its use for atrial fibrillation and flutter following open heart surgery

Fourteen patients with onset of atrial fibrillation (11) or flutter (three) and ventricular rate over 120 beats per minute following cardiac surgery were treated with intravenous (IV) doses of verapamil hydrochloride or placebo in a double-blind crossover protocol. Patients with poor left ventricular function, hypotension, atrioventricular block, and taking beta-blockers and disopyramide were excluded. The dosages were 0.075 mg/kg and 0.15 mg/kg given 15 minutes apart, with termination of study on achieving an end point (conversion to sinus rhythm or slowing of ventricular rate to below 100 beats per minute). None reached the end point with placebo but all with verapamil. Baseline ventricular rate was 144 +/- 20 beats per minute, after placebo 143 +/- 16 beats per minute, and after verapamil 89 +/- 7 beats per minute (mean +/- SD). Thus, IV verapamil briefly slows the ventricular rate of atrial tachyarrhythmias following cardiac surgery.     

Phospholipase A2 levels in acute chest syndrome of sickle cell disease

Acute chest syndrome (ACS) is associated with significant morbidity and is the leading cause of death in patients with sickle cell disease (SCD). Recent reports suggest that bone marrow fat embolism can be detected in many cases of severe ACS. Secretory phospholipase A2 (sPLA2) is an important inflammatory mediator and liberates free fatty acids, which are felt to be responsible for the acute lung injury of the fat embolism syndrome. We measured SPLA2 levels in 35 SCD patients during 20 admissions for ACS, 10 admissions for vaso-occlusive crisis, and during 12 clinic visits when patients were at the steady state. Eleven non-SCD patients with pneumonia were also evaluated. To determine if there was a relationship between sPLA2 and the severity of ACS we correlated SPLA2 levels with the clinical course of the patient. In comparison with normal controls (mean = 3.1 +/- 1.1 ng/mL), the non- SCD patients with pneumonia (mean = 68.6 +/- 82.9 ng/mL) and all three SCD patient groups had an elevation of SPLA2 (steady state mean = 10.0 +/- 8.4 ng/mL; vaso-occlusive crisis mean = 23.7 +/- 40.5 ng/mL; ACS mean = 336 +/- 209 ng/mL). In patients with ACS sPLA2 levels were 100- fold greater than normal control values, 35 times greater than values in SCD patients at baseline, and five times greater than non-SCD patients with pneumonia. The degree of SPLA2 elevation in ACS correlated with three different measures of clinical severity and, in patients followed sequentially, the rise in SPLA2 coincided with the onset of ACS. The dramatic elevation of SPLA2 in patients with ACS but not in patients with vaso-occlusive crisis or non-SCD patients with pneumonia and the correlation between levels of SPLA2 and clinical severity suggest a role for SPLA2 in the diagnosis and, perhaps, in the pathophysiology of patients with ACS.     

Asthma caused by potassium aluminium tetrafluoride: a case series

The objective of this study is to describe a case-series of potassium aluminium tetrafluoride (KAlF₄)-induced occupational asthma (OA) and/or occupational rhinitis (OR). The study involves five patients from a heat-exchanger production line who were examined (including specific inhalation challenge tests) for suspected OA and/or OR caused by a flux containing almost 100% KAlF₄ − with fluorides’ workplace air concentrations ranging between 1.7 and 2.8 mg/m³. No subject had a previous history of asthma. All five patients had a positive specific challenge test (three patients were diagnosed with OA alone, one with OR and one with both OR and OA). At the follow-up visit, after three years on average, all patients needed permanent corticosteroid therapy (four topical, one oral). After elimination from the exposure, only one of the observed subjects gave an indication of an improvement, two subjects stabilized and two worsened. Our case series focuses on the correlation between patients’ exposure to fluorides in air-conditioner production and the subsequent occurrence of OR/OA. Currently, it is uncertain whether these OR/OA were caused by hypersensitivity or irritation.     

Step On It! Impact of a Workplace New York City Taxi Driver Health Intervention to Increase Necessary Health Care Access

Objectives. We describe the impact of the Step On It! intervention to link taxi drivers, particularly South Asians, to health insurance enrollment and navigate them into care when necessary.Methods. Step On It! was a worksite initiative held for 5 consecutive days from September 28 to October 2, 2011, at John F. Kennedy International Airport in New York City. Data collected included sociodemographics, employment, health care access and use, height, weight, blood pressure, and random plasma glucose. Participants were given their results, counseled by a medical professional, and invited to participate in free workshops provided by partner organizations.Results. Of the 466 drivers participated, 52% were uninsured, and 49% did not have a primary care provider. Of 384 drivers who had blood pressure, glucose, or both measured, 242 (63%) required urgent or regular follow-up. Of the 77 (32%) requiring urgent follow-up, 50 (65%) sought medical care at least once, of whom 13 (26%) received a new diagnosis. Of the 165 (68%) requiring regular follow-up, 68 (41%) sought medical care at least once, of whom 5 (7%) received a new diagnosis.Conclusions. This study provides encouraging results about the potential impact of an easy-to-deliver, easily scalable workplace intervention with a large, vulnerable population.New York City alone has more than 50 000 yellow taxi drivers and a similar number of livery drivers.1 A large majority, 94%, are immigrants, mainly originating from India, Bangladesh, Pakistan, Haiti, and West African countries.1 Taxi drivers are often at greater risk for cardiovascular disease (CVD) and associated risk factors than the general population.2,3 Studies looking exclusively at taxi drivers have found a correlation between the occupation and myocardial infarctions, multivessel disease, obesity, insulin resistance, high blood pressure, high triglycerides, and high low-density lipoproteins.3 By nature of their occupation, drivers have a sedentary lifestyle.4,5 Sedentariness in the general population has been linked to a higher CVD mortality rate, secondary to coronary heart disease, sudden heart failure, hypertension, and diabetes.6–11 Environmental exposures are also to blame for high CVD and lung cancer risk for taxi drivers. Exposure to particulate matter, which is often found at high levels in closed vehicles, has been linked to lower heart rate variability, a predictor of CVD, and to lung cancer.12–14Other factors, such as high stress, poor working conditions, long hours, unstable income, unhealthy diet, significant concern about personal safety on the job, and institutional and organizational barriers further contribute to poorer health among taxi drivers.5,15–17 Several reports and studies on the working and living conditions of taxi drivers have been released in California; Chicago, Illinois; and New York City and described similar health profiles for this population.5,15,16 In New York City, drivers typically work 10- to 12-hour shifts 6 days a week.4,16,18 Studies have also shown that a major systems-level obstacle for taxi drivers is lack of adequate health care; 60% of taxi drivers were found to be uninsured in a Chicago study19 and 52% in a New York City study.20 The occupation-related barriers to care experienced by this largely immigrant community are further exacerbated by literacy and language barriers, financial pressures, family obligations, and cultural values.4,19,21 South Asian taxi drivers, the largest group of yellow taxi drivers in New York City, potentially face a double burden for CVD because of both the nature of their occupation and the increased CVD risk associated with South Asian ethnicity.22–27Several studies have demonstrated the successful use of occupation-based interventions to effect lifestyle changes.17,28–31 A literature review of dietary promotion programs in the workplace demonstrated that, with industry cooperation and use of a social–ecological model of intervention, worksite interventions can have gradual and favorable results.17 In one social–ecological study, changes to workplace cafeteria food service in conjunction with behavioral interventions for workers resulted in a significant increase in fruit and vegetable consumption among participants.17 Support from workplace management was crucial for the success of this program.17 Although a paucity of data exist on interventions specifically for US taxi drivers, a number of European studies have had good results for exercise and diet interventions for taxi and other drivers.29–31 A British pilot study used a peer video to encourage drivers to make healthy lifestyle changes over a 1-year study period, resulting in 73% of participating drivers reporting a significant lifestyle change, with greater physical activity, positive diet changes, and more time spent on family activities.29 Another British study used a peer education model for CVD risk education. Peer “health champions” disseminated information about free screenings and medical referrals; more than 66% of those who received medical appointments at screenings subsequently attended them.30 In Sweden, a healthy eating workplace intervention conducted at rest stops resulted in improved nutritional balance in meal choices among truck drivers.31 The results of these studies suggest that the workplace can be an effective setting for taxi driver health interventions in the United States.28The Immigrant Health and Cancer Disparities Service (IHCD) at Memorial Sloan-Kettering Cancer Center designed and implemented a taxi driver workplace health intervention, Step On It!, in 2011 at the John F. Kennedy (JFK) International Airport yellow cab holding lot in New York City. The Step On It! intervention incorporates specific components addressing drivers’ barriers to care, including

1. health insurance enrollment education and enrollment assistance to address lack of health insurance;
2. referrals to low-cost or free health clinics and hospitals to address financial barriers to obtaining health insurance;
3. referrals to culturally and linguistically appropriate care to address language and cultural barriers;
4. events held during work hours, providing a window of opportunity, and assistance with finding clinics with flexible hours, to address drivers’ long work hours; and
5. onsite health screening and counseling with triage to urgent or regular follow-up to address lack of knowledge related to current health status and need for care.

After drivers were assessed for health care access and utilization, medical history, and CVD risk factors; screened for hypertension and elevated random plasma glucose; and measured for body mass index (BMI), Step On It! used a health care access navigation and case management intervention to link drivers to health insurance enrollment and navigate them into care when necessary. We describe the impact of this intervention on the primary outcome of interest, drivers’ engagement in needed medical care.     

腹腔镜手术对不孕症患者的诊断及治疗价值研究

目的探讨腹腔镜手术对不孕症患者的诊断及治疗价值。方法回顾性分析新疆医科大学第一附属医院2010年9月-2014年5月收治的319例不孕症患者的临床资料,对所有患者行腹腔镜下诊断及相应的手术治疗(包括盆腔粘连分解、输卵管造口术、输卵管灼断术等)。结果 319例患者腹腔镜术中检查与术前子宫输卵管碘油造影结果的符合率为72.1%(230/319),其中有43例术中发现子宫肌瘤,56例术中发现输卵管系膜囊肿,8例患者术中发现子宫内膜异位症,有2例患者诊断为盆腔结核,1例术中发现结肠肌瘤(术前考虑卵巢囊肿),其余为不同程度的盆腔慢性炎症。轻度粘连69例,妊娠21例,宫外孕2例,妊娠率33.33%。中重度粘连250例,其中行灼断术34例,灼断术患者后行体外受精及胚胎移植(IVF-ET),妊娠13例,妊娠率38.23%(13/34)。其余216例,失访3例,妊娠31例,宫外孕3例、妊娠率15.9%。结论腹腔镜对诊断输卵管性不孕及盆腔疾病有重要价值,子宫输卵管造影仅能初级筛查,诊断价值有限。在治疗输卵管粘连梗阻中,腹腔镜的治疗价值有待进一步探讨,临床预后与盆腔炎症的程度有关,应个体化选择手术方案。     

Evidence for endothelium-derived relaxing factor in cultured cells

Intracellular cyclic GMP concentration was used as a biochemical indicator of endothelium-dependent and organonitrate-induced responses to these vasodilators in cultured porcine aortic smooth muscle and endothelial cells. Sodium nitroprusside (10(-6) M) caused a rapid increase in cyclic GMP levels in confluent smooth muscle cell cultures but not in confluent endothelial monolayers. Adenosine triphosphate (10(-4) M) and methacholine (10(-5) M), two agents that elicit endothelium-dependent relaxation in intact vessels, failed to raise cyclic GMP concentrations in muscle or endothelial cultures alone. When the cell types were grown together in mixed culture, however, treatment with adenosine triphosphate or methacholine induced an elevation in intracellular cyclic GMP levels. These findings suggest that mixed cultures of arterial smooth muscle and endothelial cells can be used to study the phenomenon of endothelium-dependent responses in arterial smooth muscle.     

Desensitization of the cAMP system in mouse Leydig cells by hCG, cholera toxin, dibutyryl cAMP and cAMP: localization of the 'lesion' to the guanine nucleotide regulatory protein-adenylate cyclase complex

The mechanism of hCG-induced desensitization of the cAMP system was studied in Percoll-purified mouse Leydig cells. Pretreatment of Leydig cells with hCG resulted in a time- and dose-dependent decrease in the capacity of hCG-induced cAMP formation. Maximal desensitization (approximately 90%) was induced by only partial prior stimulation. Desensitization, however, was not observed without a prior increase in cAMP or testosterone production. Pretreatment of the cells with N6,O2'-dibutyryl cAMP (DBcAMP) also induced a dose- and time-dependent densensitization. cAMP was only effective in the presence of the phosphodiesterase inhibitor 1-methyl-3-isobutylxanthine (MIX). Cholera toxin desensitized the hormone-induced cAMP response as drastically as hCG. Cholera toxin was unable to reverse the refractory state induced by one of the agonists. hCG-induced desensitization was not associated with a loss in [125I]hCG binding or an increase in maximal phosphodiesterase activity, and appeared not to be dependent on protein synthesis. Membranes from hCG, cholera toxin of DBcAMP-desensitized cells showed an impaired adenylate cyclase activity in response to hCG, hCG plus beta-gamma-imidoguanosine 5'-triphosphate (GPPNP) and NaF. In conclusion, hCG-induced desensitization of the adenylate cyclase system in mouse Leydig cells can be mimicked by cholera toxin, DBcAMP and cAMP, indicating a cAMP-mediated process. The site of the 'lesion' has to be localized to the guanine nucleotide regulatory protein-adenylate cyclase complex rather than to its uncoupling from the hormone receptor.