MRI reveals the in vivo cellular and vascular response to BEZ235 in ovarian cancer xenografts with different PI3-kinase pathway activity

Background:

The phosphoinositide-3 kinase (PI3K) pathway is an attractive therapeutic target. However, difficulty in predicting therapeutic response limits the clinical implementation of PI3K inhibitors. This study evaluates the utility of clinically relevant magnetic resonance imaging (MRI) biomarkers for noninvasively assessing the in vivo response to the dual PI3K/mTOR inhibitor BEZ235 in two ovarian cancer models with differential PI3K pathway activity.

Methods:

The PI3K signalling activity of TOV-21G and TOV-112D human ovarian cancer cells was investigated in vitro. Cellular and vascular response of the xenografts to BEZ235 treatment (65 mg kg⁻¹, 3 days) was assessed in vivo using diffusion-weighted (DW) and dynamic contrast-enhanced (DCE)-MRI. Micro-computed tomography was performed to investigate changes in vascular morphology.

Results:

The TOV-21G cells showed higher PI3K signalling activity than TOV-112D cells in vitro and in vivo. Treated TOV-21G xenografts decreased in volume and DW-MRI revealed an increased water diffusivity that was not found in TOV-112D xenografts. Treatment-induced improvement in vascular functionality was detected with DCE-MRI in both models. Changes in vascular morphology were not found.

Conclusions:

Our results suggest that DW- and DCE-MRI can detect cellular and vascular response to PI3K/mTOR inhibition in vivo. However, only DW-MRI could discriminate between a strong and weak response to BEZ235.     

A Case of Upper Limb Compartment Syndrome following Snake Envenomation Measure Twice,Cut Once

We report a case of a 16-year old male patient who sustained a poisonous bite from a mapepire balsain snake on the dorsum of his left hand. The subject presented within one hour of envenomation and subsequently developed clinical features of acute compartment syndrome in the involved upper limb. Early diagnosis and emergency fasciotomy effectively treated his condition. Aggressive physiotherapy coupled with this ensured best functional outcome.     

Vascular air embolism: A rare complication of nasal CPAP

Abstract: A preterm infant developed bilateral tension pneumothoraces and extensive vascular air embolism 6 h after being commenced on nasal continuous positive airway pressure (CPAP). Neonatal clinicians should be aware that catastrophic vascular air embolism could occur in infants receiving nasal CPAP, a modality of respiratory support conventionally considered non-invasive and 'safe'.     

Systematic review of chronic pain in persons with Marfan syndrome

The purpose of this study was to explore the literature on chronic pain in adults with Marfan syndrome (MFS), critically appraising and synthesizing relevant literature. A systematic review was conducted by searching the published literature databases using available medical, physical, psychological, social databases and other sources. All studies that addressed pain in MFS, published in peer‐reviewed journals were assessed. Of 351 search results, 18 articles satisfied the eligibility criteria. All studies were cross‐sectional and quantitative; no randomized controlled trials or intervention studies were found. Most studies had small sample sizes, low response rates and mainly dealt with other aspects of the diagnosis than pain. Only one article dealt mainly with pain. The research on chronic pain in MFS is limited in size and quality. Despite these limitations, studies describe that the prevalence of pain in patients with MFS is high, varying from 47 to 92% and affecting several anatomic sites. In addition, chronic pain limits daily function and few studies describe treatment options for pain in patients with MFS. Research is needed to obtain more evidence‐based knowledge for developing more appropriate rehabilitation programs for people with MFS.     

Massive subdural haematoma: An unusual complication of septicaemia in preterm very low birthweight infants

Non-traumatic massive subdural haematoma is a rare condition in newborn infants and is usually associated with hereditary coagulation disorders or congential vascular malformation. Its occurrence in preterm very low birthweight infants secondary to systemic bacterial infection has not been reported. We describe two extremely preterm neonates who developed massive subdural haematoma as a result of Gram-negative septicaemia and disseminated intravascular coagulation. Both infants suffered severe parenchymal cerebral injury and hydrocephalus. Clinicians should be aware of this unusual and catastrophic complication if a very low birthweight infant with severe sepsis and disseminated intravascular coagulation suddenly deteriorates despite successful treatment with antibiotics. Radiological imaging by cranial ultrasound or computed tomography scanning should be routinely considered in all such infants for the detection of intracranial bleeding.     

Primary prevention in a high-risk group: smoking habits in adolescents with homozygous alpha-1-antitrypsin deficiency (ATD)

The serious form of alpha-1-antitrypsin deficiency (ATD) Pi ZZ strongly predisposes the individual for pulmonary emphysema and premature death in adulthood, especially if exposed to tobacco smoking. General screening of all new-born children was conducted in Sweden during 1972–1974, the major purpose being to reduce exposure of the child to parental smoking while growing up and to prevent the child from starting to smoke. Sixty-one children with ATD neonatally identified through mass-screening, and their families, have been compared with a demographically matched control group regarding smoking habits, as studied through interviews and questionnaires on two occasions. When the children were 5–7 years old, the smoking rates among parents of the ATD children and especially among the ATD fathers exceeded smoking rates for controls. Thirteen years later no differences in parental smoking were found between the groups. At 18–20 years of age the ATD children reported smoking significantly less than the control children (p < 0.05). From the perspective of prevention, the goal of the neonatal screening to reduce the smoking rates among the parents of the ATD children was not attained, while it was achieved among the ATD children. The results indicate that a screening program with early detection of ATD effectively prevents adolescent children from starting to smoke. From ethical, medical and psychological points of view, a voluntary screening program for ATD in pre-adolescence is recommended.     

Clinical effectiveness and safety experience with efalizumab in the treatment of patients with moderate-to-severe plaque psoriasis in Taiwan: results of an open-label, single-arm pilot study

Background No clinical trial of efalizumab has been conducted in Asia. Objective To determine the efficacy and safety of efalizumab in Taiwanese patients with psoriasis. Methods This is an open‐label, single‐arm pilot study conducted at two centres. Patients were given 1 mg/kg efalizumab subcutaneously once a week for 12 weeks and were then followed up for a further 12 weeks. Results A total of 49 patients participated in the study. The median improvement in Psoriasis Area and Severity Index (PASI) during the treatment period was 19.6%, and a ≥ 50% improvement in PASI was seen in 20.4%. Rebound was seen in 17.8% of patients, and anti‐efalizumab antibodies were detected in 41% of patients. The most frequent adverse events were headache (34.7%), arthralgia/arthritis (28.6%), psoriasis events (new form/exacerbation; 26.5%) and pruritus (22.4%). Conclusions This small pilot study indicated that efalizumab was effective in improving psoriasis symptoms in Taiwanese patients, with no new safety issues identified.