Calcium response in osteocytic networks under steady and oscillatory fluid flow

The fluid flow in the lacunar-canalicular system of bone is an essential mechanical stimulation on the osteocyte networks. Due to the complexity of human physical activities, the fluid shear stress on osteocyte bodies and processes consists of both steady and oscillatory components. In this study, we investigated and compared the intracellular calcium ([Ca(2+)](i)) responses of osteocytic networks under steady and oscillatory fluid flows. An in vitro osteocytic network was built with MLO-Y4 osteocyte-like cells using micro-patterning techniques to simulate the in vivo orderly organization of osteocyte networks. Sinusoidal oscillating fluid flow or unidirectional steady flow was applied on the cell surface with 2Pa peak shear stress. It was found that the osteocytic networks were significantly more responsive to steady flow than to oscillatory flow. The osteocytes can release more calcium peaks with higher magnitudes at a faster speed under steady flow stimulation. The [Ca(2+)](i) signaling transients under the steady and oscillatory flows have significantly different spatiotemporal characters, but a similar responsive percentage of cells. Further signaling pathway studies using inhibitors showed that endoplasmic reticulum (ER) calcium store, extracellular calcium source, ATP, PGE(2) and NO related pathways play similar roles in the [Ca(2+)](i) signaling of osteocytes under either steady or oscillating flow. The spatiotemporal characteristics of [Ca(2+)](i) transients under oscillating fluid flow are affected more profoundly by pharmacological treatments than under the steady flow. Our findings support the hypothesis that the [Ca(2+)](i) responses of osteocytic networks are significantly dependent on the profiles of fluid flow.     

Parkinson's disease symptoms —'patients' perceptions

Self-assessment is significant for the accurate evaluation of patient's needs. This study examined the frequency and severity of symptoms suggested by the literature and by specialists as bothering Parkinson's patients. Four categories of symptoms were examined: (a) motor disability or activity loss, (b) mental change, (c) psychosocial difficulties, and (d) nonspecific symptoms. The findings show that there was correspondence between expert judgements and subject's reports regarding symptoms such as dyskinesia/tremor as well as walking, freezing gait, and changing position. Symptoms such as dressing self, getting in/out of bed, morning stiffness and deficit in cognitive sequencing, which experts described as characteristic of Parkinson's disease patients, bothered subjects less. In general, patient's mental and psychosocial symptoms were higher in their frequencies and perceived severity than problems of performing activities of daily living.     

Cerebral germinoma with marked granulomatous inflammation: Granulomatous germinoma

Cerebral germinomas with granulomatous inflammation are rare lesions that can present diagnostic difficulties. Four cases (two male and two female) of germinomas with pronounced inflammatory reaction are presented. The age ranged from 14 to 21 years (mean 18). Three patients with vision defects had masses around the sellar region, and a long duration of symptoms (2, 4 and 5 years). The fourth patient had a mass in the temporal lobe; she had convulsions and the duration of her symptoms was short (3 weeks). All lesions consisted of inflammatory changes with scattered neoplastic germinoma cells that expressed placental alkaline phosphatase. The inflammation area occupied more than two-thirds of the mass, and consisted of macrophages and their syncytial forms of mutinucleated giant cells, T-cells, B-cells, plasma cells, fibroblasts, and histiocytes or glial cells. Sarcoid granulomata were frequently seen, and multinucleated giant cells with Schaumann's bodies were also visible. The term ‘cerebral granulomatous germinoma’ is proposed for these unusual tumors. Moreover, it is likely that the study of cerebral granulomatous germinoma may provide some important clues towards the understanding of granulomatous inflammation in organs in general.     

Leadership style and choice of strategy in conflict management among Israeli nurse managers in general hospitals

AIMS: To identify conflict mode choices of head nurses in general hospitals and examine the relationship between leadership style, choice of strategy in handling conflicts and demographic characteristics. BACKGROUND: Nurse managers deal with conflicts daily. The choice of conflict management mode is associated with managerial effectiveness. The ability to creatively manage conflict situations, towards constructive outcomes is becoming a standard requirement. METHODS: Head nurses (N = 60) in five general hospitals in central Israel were surveyed, using a 3-part questionnaire: The Thomas-Kilmann Conflict Mode Instrument, the Multi-factor Leadership Questionnaire, Form 5X-Short (MLQ 5X) and demographic data. RESULTS: Head nurses perceive themselves significantly more as transformational leaders than as transactional leaders. Compromise was found to be the most commonly used conflict management strategy. Approximately half of the nurses surveyed used only one mode in conflict management. Transformational leadership significantly affected the conflict strategy chosen. CONCLUSION: Head nurses tend to choose a conflict-handling mode which is concerned a form of a Lose-Lose approach. Preparation in conflict management should start from undergraduate education.     

Profile of sight‐threatening infectious keratitis: a prospective study

Purpose: To prospectively study patients presenting with sight‐threatening corneal ulcers with a view to identify the predisposing factors, causative organisms, clinical signs and treatment outcomes. Methods: Prospectively, over 3‐year period, all cases with serious infective keratitis presenting to Queens Medical Hospital in Nottingham, UK, were recruited. Detailed information on the aetiology, culture results, signs & symptoms, the treatment given and the patient’s response was collected and statistically analysed. Results: One hundred and forty‐three eyes of 129 patients were enrolled. Thirty‐one patients were managed as out‐patients, and 98 were treated as in‐patients. The mean duration of admission was 9 ± 13 days but was significantly higher in older patients and in Acanthamoeba keratitis cases. The important risk factors were ocular surface disease (32%), contact lens wear (26%) and previous ocular surgery (20%). Old age, deep infiltration, steroid use and poor initial vision were risk factors for prolonged course of treatment in bacterial keratitis. Corneal scrapings were done in 89% of the cases, but positive results were obtained only in 41.7%. Staphylococcus aureus was the most common isolated bacteria (18.8%). Acanthamoeba and Pseudomonas aeruginosa were the second and third common causative organisms (16.6% and 15%, respectively). Overall, 8.3% needed corneal grafting, which survived in 83.3% and eradicated infection in 100%. Conclusion: Microbial keratitis is an important cause of ocular morbidity. Previous ocular disease is an important predisposing factor. Old age, steroid use and poor presenting visual acuity are important prognostic indicators. Corneal grafting is an effective option for managing recalcitrant corneal infections.     

Intra-lesional 5 fluorouracil for the management of recurrent pterygium

Aim

Recurrence is the most common complication arising from pterygium surgery. The aim of this study was to investigate the effectiveness of 5 fluorouracil (5FU) in halting the recurrence of pterygium after surgical excision.

Methods

A retrospective review of patients treated for pterygium recurrence was carried out. Patients with recurrent (secondary) pterygium were treated with multiple weekly intra-lesional injections of 0.1–0.2 ml (2.5–5 mg) 5FU post-operatively depending on the size of the recurrence. The treatment was started within 1 month from the date of recurrence. The time from surgery to start of recurrence, previous treatment modalities, and number of recurrences were documented. The number of injections required to induce arrest of progression and/or regression of vascularity and fleshiness of the pterygium and any complications related to 5FU treatment were examined.

Results

Fifteen eyes from 14 patients with recurrent pterygium treated with intra-lesional 5FU injections were analysed. Three of the 15 eyes had undergone a secondary excision and 12 had undergone a primary excision. In all, 93.3% of patients showed regression of the fibrovascular tissue (thickness and vascularity) and arrest of progression following a dose of 0.1–0.2 ml (2.5–5 mg) 5FU. Twelve eyes required three injections or fewer, whereas one patient required eight injections. This beneficial effect was maintained over an average follow-up period of 17 months. No complications from 5FU were observed.

Conclusion

The use of weekly intra-lesional 5FU injections for the treatment of recurrent pterygium is safe and effective in limiting the progression and inducing the regression of recurrent pterygium. The number of injections can be tailored according to clinical need.     

Dihydropyridines and multidrug resistance: previous attempts, present state, and future trends

Multidrug resistance is defined as the resistance of a tumor cell to the cytotoxic action of divergent drugs used in chemotherapy. Dihydropyridines are a class of calcium channel antagonists that were discovered to have a multidrug resistance reversing effect and prompted investigations resulting in the synthesis of hundreds of new derivatives. Most of the investigators tried to achieve two goals: a decrease in Ca2(+) channel-blocking activity and an increase in the multidrug resistance reversing effect. Most of the synthesized compounds failed in the later stages of studies especially in clinical trials because of pharmacokinetic or pharmacodynamic limitations. Therefore, it will be necessary to include new methods, such as combinatorial synthesis, and, more importantly, to apply computational methods based on global structure-activity relationship models that consider all problems. Moreover, some compounds should be synthesized that are effective on several multidrug resistance targets.