Intravital imaging reveals p53-dependent cancer cell death induced by phototherapy via calcium signaling

One challenge in biology is signal transduction monitoring in a physiological context. Intravital imaging techniques are revolutionizing our understanding of tumor and host cell behaviors in the tumor environment. However, these deep tissue imaging techniques have not yet been adopted to investigate the second messenger calcium (Ca²⁺). In the present study, we established conditions that allow the in vivo detection of Ca²⁺ signaling in three-dimensional tumor masses in mouse models. By combining intravital imaging and a skinfold chamber technique, we determined the ability of photodynamic cancer therapy to induce an increase in intracellular Ca²⁺ concentrations and, consequently, an increase in cell death in a p53-dependent pathway.     

Chronic lymphocytic leukemia revealed by a branulomatous zosteriform eruption

A 70-year-old woman presented with an atypical erythematopapular zosteriform eruption of 3 weeks' duration. The patient had no history of previous vesicular eruption. She developed a painful burning sensation on the neck. Clinical examination revealed a cluster of small erythematous firm papules and plaques in a zosteriform distribution on the left ear, face, neck, and shoulder (Figure 1A). The lesions were unilateral and did not cross the midline. Multiple cervical and axillary lymph nodes were palpable. Laboratory tests revealed an increase in white blood cells of 25,000/mm3, with 17,910/mm3 lymphocytes and a normal range of hemoglobin, platelets, creatinine, and liver enzymes. Erythrocyte sedimentation rate was 87 mm. Blood smear results showed small, morphologically mature lymphocyte cells. In immune phenotyping, lymphocyte cells co-express CD5 and B-cell-surface antigens CD19 and CD23, as well as a restriction of kappa immunoglobulin light chains. The cells were CD22-, CD79b-, CD38-, CD10-, CD25- and FMC7-. Computed thoracoabominal tomography revealed cervical, mediastinal, abdominal, and pelvic adenopathy confirming the diagnosis of B-cell chronic lymphocytic leukemia (B-CLL) stage B. Histology of a skin biopsy from a papule showed a dense nodular granulomatous infiltrate in the dermis (Figure 2A). The infiltrate contained epithelioid and giant cells surrounded by lymphocytes and plasma cells. Small monomorphic lymphocytes without mitotic figures predominated (Figure 2B). The epidermis was irregularly thickened. Immunohistology revealed a polymorphous infiltrate with a phenotype of reactive T lymphocytes (CD3, CD5 positive) (Figure 2C), B lymphocytes (CD20 positive) (Figure 2D). Epithelioid and giant cells were positive for CD68 (Figure 2E). A latent herpes zoster infection with granulomatous reaction at the site ofzoster lesions was highly suspected as the patient reported a unilateral burning sensation without a history of vesicular zosteriform eruption. She received treatment with intravenous acyclovir 10 mg/kg every 8 hours. The papular lesions resolved markedly (60%) on macular plaques at the end of the treatment. Following topical treatment with corticosteroids, the lesions healed completely within 4 weeks (Figure 1B). Concerning leukemia, our patient was monitored without therapy by the hematologist.     

Will the implementation of the 2007 National Institute for Health and Clinical Excellence (NICE) guidelines on childhood urinary tract infection (UTI) in the UK miss significant urinary tract pathology?

What's known on the subject? and What does the study add? Most centres continue to investigate children extensively after a urinary tract infection. These investigations are invasive, time consuming and expensive and despite their widespread application they have not had a significant impact on the rates of chronic renal failure secondary to infection. Despite this evidence the National Institute for Health and Clinical Excellence (NICE) guidelines generated significant controversy that abnormalities would be missed, placing children at increased risk of renal injury, thus reducing their implementation. Significant underlying abnormalities of the urinary tract will not be missed if the NICE guidelines are followed. This will reduce the unpleasant investigations that children will be subjected to and it should lead to considerable cost savings. The NICE guidelines are safe and should be widely implemented.

OBJECTIVE

• ? To investigate whether the implementation of the August 2007 National Institute for Health and Clinical Excellence (NICE) guidelines would miss significant urinary tract pathology in children with urinary tract infection (UTI).

PATIENTS AND METHODS

• ? All ultrasound (US) performed in children aged >6 months, during the year 1 August 2006 to 31 July 2007 for UTI, were retrospectively studied.
• ? Each US scan in the study population of 346 was categorised dependent on whether it was appropriate or inappropriate to have been performed under the new guidelines and whether the US scan was normal or abnormal.
• ? The records of each patient with an inappropriate abnormal US scan were re‐analysed to see if patient management was affected by the US scan.
• ? In 2011 patients with an original inappropriate abnormal US scan were re‐evaluated to identify if any had presented with further urinary pathology.

RESULTS

• ? In accordance with the NICE guidelines patients were divided by age.
• ? Children aged 0.5–3 years: 78/95 (82%) US scans were inappropriate of which 12 (15%) were abnormal and four of these had a further documented UTI. After careful assessment of the US abnormalities it was judged that only one would have benefited from the initial US scan.
• ? Children aged >3 years: 146/251 (58%) US scans were inappropriate of which 21(14%) were abnormal and six of these (29%) had a further documented UTI. After careful assessment of the US abnormalities it was judged that only three of 21 (14%) would have benefited from the initial US scan.

CONCLUSIONS

• ? The vast majority of anomalies detected on the inappropriate US scans were of little clinical significance.
• ? It is difficult to identify any patient who would have been truly disadvantaged if the US scan had not been performed after the initial UTI.
• ? The NICE guidelines are safe to follow.

     

Clonidine does not improve quality of ropivacaine axillary brachial plexus block in children

Background: The addition of clonidine to peripheral nerve blocks is controversial in children. Objective: The aim of our study was to evaluate the effect of clonidine added to ropivacaine in pediatric axillary brachial plexus block (ABPB). Methods: Children aged 1–6 years, scheduled to undergo forearm or hand surgery, were recruited into this prospective, double‐blind controlled trial. Patients were randomly allocated to receive an ABPB either with ropivacaine 0.2% 0.4 ml·kg^?1 plus saline in 1 ml (RS) or ropivacaine 0.2% 0.4 ml·kg^?1 plus clonidine 1 μg·kg^?1 in 1 ml (RC). Primary endpoints were quality of postoperative analgesia as assessed by pain scores and total 24‐h postoperative analgesia requirements. Secondary outcomes were time to first analgesia request and duration of motor blockade. Results: Sixty patients were recruited (n = 30 per group) into the study. Pain scores were comparable throughout the first 24 h between the two groups. Ten children in the (RS) and six in (RC) groups required supplementary analgesia during the first 24 h (P = 0.24). Children who required further analgesia did so after 288 ± 94 min in the (RS) and 437 ± 204 min in the (RC) group (P = 0.06). There was no difference in the duration of motor block [186 ± 71 and 154 ± 56 min, P = 0.12 for (RS) and (RC), respectively]. Conclusion: Ropivacaine (0.2% 0.4 ml·kg^?1) for ABPB provides sufficient postoperative analgesia in children scheduled for forearm or hand surgery. The addition of clonidine to ABPB does not improve overall postoperative analgesia but may increase the time to first analgesia request.