Decreased leukotriene B4 synthesis in smokers' alveolar macrophages in vitro

Recent studies have shown that alveolar macrophages (AM) are able to release leukotrienes (LTs). Since cigarette smoking inhibits the cyclooxygenase pathway of arachidonic acid metabolism in the AM, we evaluated the LT production by AM from smokers and nonsmokers. AM were obtained from 35 volunteers, 16 nonsmokers, and 19 smokers. The cells were incubated under various conditions including stimulation with 30 microM arachidonic acid, 2 microM ionophore A23187, or both. Each experiment was performed in parallel using cells from a smoker and a nonsmoker. Lipoxygenase products were analyzed by reverse-phase high performance liquid chromatography. After stimulation, nonsmokers' AM produced LTB4 and 5-hydroxy-eicosatetraenoic acid (5-HETE). In incubations of AM with arachidonic acid and ionophore, the amounts of products formed were: LTB4, 317 +/- 56 pmol/10(6) cells and 5-HETE, 1,079 +/- 254, mean +/- SEM. No metabolites were generated under control conditions (no stimulation). In all incubations performed, the peptido-LTs (LTC4, LTD4, and LTE4) were undetectable. In comparison with AM from nonsmokers, those from smokers showed a 80-90% reduction of 5-HETE and LTB4 synthesis (P less than 0.05 to P less than 0.001 according to stimulatory conditions). This defective lipoxygenase metabolite production in AM from smokers was observed over a wide range of stimuli concentrations and incubation times; AM from smokers also had lower levels of intracellular (esterified) 5-HETE than nonsmokers' AM. We also studied blood polymorphonuclear leukocytes (PMNL) and no difference in the synthesis of 5-lipoxygenase products in these cells was noticed between smokers and nonsmokers. These data show that cigarette smoking causes a profound inhibition of the 5-lipoxygenase pathway in AM but not in blood PMNL.     

Immunoprofile of the adenomatoid odontogenic tumor

This study was focused on the immunohistochemical profile of the adenomatoid odontogenic tumor. A Pub/Medline search revealed a number of immunohistochemical studies including cytokeratin profiles, extracellular matrix proteins, Integrins, ameloblast‐associated proteins resorption regulators (RANK, RANKL), p53, PCNA, MDM2 protein, cyclin D1, Ki‐67, Bcl‐2 metallothionein, metalloproteinases, D56 hepatocyte growth factor, c‐met, DNA methyltransferase, podoplanin, TGF‐βI, Smad‐2/3, Smad‐I‐5/‐8, Smad 4, beta‐ catenin, calretinin, and clonality. Careful interpretation of the findings indicates that the adenomatoid odontogenic tumor may be more of a hamartomatous than neoplastic nature.     

Robot-Assisted Transaxillary Thyroid Surgery in the United States: Is it Comparable to Open Thyroid Lobectomy?

Background  

The purpose of this study was to compare the outcome of robot-assisted transaxillary thyroid surgery (RATS) to the standard open technique for thyroid lobectomy in the U.S. population.     

Breast Surgery Outcomes as Quality Measures According to the NSQIP Database

Background

The National Surgical Quality Improvement Program (NSQIP) is a risk-adjusted database designed to benchmark quality initiatives. NSQIP captures uniform morbidity variables for all operations and calculates expected morbidity probabilities. Given the frequent need for reoperation following breast-conserving surgery (BCS) and mastectomy, we hypothesized that NSQIP may inaccurately reflect surgical morbidity after breast cancer operations.

Methods

Using the 2008 NSQIP database, we identified 24,447 breast surgery patients. We calculated the observed versus expected (O/E) morbidity ratios, compared them to other general surgery procedures, and analyzed the O/E morbidity ratios among benign and malignant breast diagnoses.

Results

The NSQIP database shows that breast surgery has an O/E morbidity ratio of 3.11, which is higher than other general surgery procedures. Additionally, breast operations for malignancy have higher O/E morbidity ratios (3.22) than those performed for benign disease (2.59). Analysis of malignant patients by CPT code revealed that BCS patients had an O/E morbidity ratio of 7.75 and attributed 89?% of morbidity to reoperation, whereas mastectomy patients had an O/E morbidity ratio of only 1.7. Elimination of the reoperation variable from morbidity calculations in breast surgery reduces the O/E morbidity ratio to less than expected in all breast procedures.

Discussion

Breast surgery has a higher O/E morbidity ratio than other general surgery procedures. Reoperations are expected in BCS for positive margins and in mastectomy for completion ALND. Breast surgeons should advocate for benchmarking by surgical site-specific metrics, because current NSQIP criteria may negatively affect the quality assessment of high-volume breast centers.     

Unmet support needs of early-onset dementia family caregivers: a mixed-design study

Background

Though advances in knowledge and diagnostics make it possible today to identify persons with early-onset dementia or a related cognitive disorder much sooner, little is known about the support needs of the family caregivers of these persons. The aim of this study was to document the unmet support needs of this specific group of caregivers. This knowledge is essential to open avenues for the development of innovative interventions and professional services tailored to their specific needs.

Methods

This study was conducted using a mixed research design. Participants were 32 family caregivers in their 50s recruited through memory clinics and Alzheimer Societies in Quebec (Canada). The Family Caregivers Support Agreement (FCSA) tool, based on a partnership approach between caregiver and assessor, was used to collect data in the course of a semi-structured interview, combined with open-ended questions.

Results

The unmet support needs reported by nearly 70% of the caregivers were primarily of a psycho-educational nature. Caregivers wished primarily: (1) to receive more information on available help and financial resources; (2) to have their relatives feel valued as persons and to offer them stimulating activities adjusted to their residual abilities; (3) to reduce stress stemming from their caregiver role assumed at an early age and to have the chance to enjoy more time for themselves; and (4) to receive help at the right time and for the help to be tailored to their situation of caregiver of a young person.

Conclusions

Results show numerous unmet support needs, including some specific to this group of family caregivers. Use of the FCSA tool allowed accurately assessing the needs that emerged from mutual exchanges. Avenues for professional innovative interventions are proposed.

     

Comparison of thrombin and ristocetin in the interaction between von Willebrand factor and platelets

It is known that the antibiotic ristocetin exposes the platelet membrane receptor for factor VIII/von Willebrand glycoprotein (FVIII/vWF). Recent reports suggest that low concentrations of thrombin also cause platelet membrane receptors to become available for FVIII/vWF. As a consequence, the suspicion has been raised that thrombin provides similar or equivalent activity in vivo to that observed for ristocetin under in vitro conditions. In this study, we quantitated the extent to which thrombin promotes the binding of FVII/vWF to platelets and determined whether or not this interaction initiates or complements platelet aggregation. With ristocetin present, the amount of 125I-FVIII/vWF that became platelet-bound correlated closely with the onset, rate, and extent of platelet aggregation. In contrast, at every thrombin concentration tested, the amount of 125I- FVIII/vWF that specifically bound to platelets was about 6% of that observed with ristocetin. Significantly, FVIII/vWF did not augment the rate of aggregation of platelets in response to thrombin or initiate platelet aggregation when subaggregating doses of thrombin were used. These observations indicate that the minimal association that occurs between FVIII/vWF and the platelet membrane in the presence of thrombin does not correlate with platelet aggregation and therefore is not analogous to the effects of ristocetin. Whether the low level of binding relates to another process, such as platelet-endothelial interactions, remains unknown.