Bleomycin and scuba diving: to dive or not to dive?

Bleomycin is to treat patients with testicular cancer and lymphoma. Bleomycin can bind to DNA and chelate iron. The resulting complex can form an intermediate capable of interacting with oxygen to produce reactive oxygen species, particularly superoxide. Administrating high-inspired oxygen concentrations (e.g. during anaesthesia or acute illness) has been reported to exacerbate pulmonary injury. The duration of risk after bleomycin chemotherapy is unknown. Here we discuss our advice to a young male patient, who was successfully treated with bleomycin for testicular cancer, concerning the safety to return to scuba diving. Since scuba divers are exposed to high partial oxygen pressures (depending on the depth of the dive) we discouraged this patient from resuming scuba diving.     

Clinicopathological and radiological study of Egyptian β-thalassemia intermedia and β-thalassemia major patients: relation to complications and response to therapy

The clinico epidemiological characteristics, frequency of complications, and response to various therapeutic modalities in 80 Egyptian β-thalassemia intermedia (β-TI) patients were compared with 70 β-thalassemia major (β-TM) patients. β-Thalassemia intermedia patients had a higher incidence of left atrium dilatation, right ventricular dilatation and pulmonary hypertension, whereas, β-TM patients showed a higher incidence of left ventricular (LV) dilatation, restrictive LV filling and impaired LV contractility, with an overall higher incidence of heart disease (p <0.001). Short stature, delayed puberty, osteoporosis, bone fractures, diabetes mellitus and viral hepatitis was frequently observed in β-TM patients compared with β-TI patients (p <0.05). Administration of hydroxyurea (HU) alone was associated with significant improvement in hematological parameters and quality of life for β-TI patients. In conclusion, the risk of complications still burdens the life of Egyptian thalassemia patients and their frequency varies between β-TI and β-TM. We provide evidence that calls for the use of HU in β-TI patients.     

Interventions to improve β-cell mass and function

Diabetes mellitus (T2DM) has become an epidemiologically important disease worldwide and is also becoming a great matter of concern due to the effects associated with it like: high morbidity, elevated health care cost and shortened life span. T2DM is a chronic metabolic disease characterized by insulin resistance as well as β-cell dysfunction. It is widely accepted that in the face of insulin resistance, euglycemia can be maintained by increase in pancreatic β-cell mass and insulin secretion. This compensation is largely due to enhanced secretion of insulin by the β-cell mass, which is present initially, and thereby subsequent increases in β-cell mass provide additional insulin secretion. However, the mechanism by which β-cell anatomical plasticity and functional plasticity for insulin secretion is coordinated and executed in different physiological and pathophysiological states is complex and has been poorly understood. As the incidence of T2DM continues to increase at an alarming rate, it is becoming imperative to shift the research focus towards the β-cell physiology where identification of novel pathways that influence the β-cell proliferation and/or contribute to increase insulin secretion has the potential to lead to new therapies for preventing or delaying onset of disease.     

Diabetes and the metabolic syndrome--when is it best to intervene to prevent?

In addition to microvascular complications, patients with type 2 diabetes are at increased risk of cardiovascular disease (CVD) and mortality. An important initial step in reducing the overall burden of CVD, as well as other diabetes complications, is to prevent progression to diabetes in individuals at risk. A number of studies have indicated the increased presence of both established and emerging cardiovascular risk factors associated with the metabolic syndrome in individuals before the onset of diabetes. First-line therapy in the treatment of the metabolic syndrome risk factors is lifestyle intervention, which can be highly successful in preventing or delaying progression to overt diabetes, but on its own may not achieve and/or maintain adequate risk reduction. In this case, individuals need to be identified and treated with appropriate pharmacological interventions. The data are unequivocal in the importance of the timely identification of at-risk subjects, and implementation of effective treatment strategies, which could potentially reduce diabetes- and CVD-related morbidity and mortality.     

Inflammation and cancer: back to Virchow?

The response of the body to a cancer is not a unique mechanism but has many parallels with inflammation and wound healing. This article reviews the links between cancer and inflammation and discusses the implications of these links for cancer prevention and treatment. We suggest that the inflammatory cells and cytokines found in tumours are more likely to contribute to tumour growth, progression, and immunosuppression than they are to mount an effective host antitumour response. Moreover cancer susceptibility and severity may be associated with functional polymorphisms of inflammatory cytokine genes, and deletion or inhibition of inflammatory cytokines inhibits development of experimental cancer. If genetic damage is the "match that lights the fire" of cancer, some types of inflammation may provide the "fuel that feeds the flames". Over the past ten years information about the cytokine and chemokine network has led to development of a range of cytokine/chemokine antagonists targeted at inflammatory and allergic diseases. The first of these to enter the clinic, tumour necrosis factor antagonists, have shown encouraging efficacy. In this article we have provided a rationale for the use of cytokine and chemokine blockade, and further investigation of non-steroidal anti-inflammatory drugs, in the chemoprevention and treatment of malignant diseases.     

Why and how to treat Ph-like ALL?

Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL), or BCR-ABL1-like ALL, is a high-risk subtype of B-cell precursor ALL characterized by a gene expression profile similar to Ph-positive ALL, a high frequency of IKZF1 alterations, and poor outcome. The prevalence of Ph-like ALL is common among all ages, ranging from 10% to 15% in children to over 25% in young adults. Patients with Ph-like ALL harbor a diverse range of genetic alterations that activate cytokine receptor and kinase signaling and can be targeted with tyrosine kinase inhibitors. The majority of Ph-like ALL alterations are divided into two main groups based on activation of ABL-class or JAK-STAT alterations. Accordingly, preclinical studies and anecdotal reports suggest patients harboring ABL-class fusions are candidates for ABL1-inhibitors, whilst alterations activating the JAK-STAT pathway may be amenable to treatment with JAK inhibitors. Diagnostic screening approaches and precision medicine trials are now being developed and implemented to test the efficacy of targeted therapy with a backbone of chemotherapy, similar to the treatment of Ph-positive ALL.     

Resistance to obesity and resistance to atherosclerosis: Is there a metabolic link?

AimThis review deals with the question whether resistance to obesity affects resistance to atherosclerosis.Data synthesisResistance to diet-induced obesity in inbred mouse strains involves an adequate response to Leptin, the main regulator of the energy balance cycle. Leptin, an adipokine with both central and peripheral targets, regulates food intake and energy expenditure. Adequate response to leptin involves repression of stearoyl-CoA desaturase, activation of Amp-activated protein-kinase and uncoupling proteins, resulting in fatty acid oxidation and energy expenditure. Most of the obesity-resistant strains are also resistant to atherosclerosis, but so far no information concerning the response to the leptin cycle is available in these strains when bred onto a LDLR^−/− or apoE^−/− background. Recent studies in mouse strains on an atherosclerosis permissive background have identified genetic links between obesity and atherosclerosis. Moreover, information derived from studies on mice was applied in order to learn about the metabolic effectors in humans and is included in this review.ConclusionsThe data presented in this review provide recent information concerning metabolic pathways that play an important role in the regulation of energy balance, a prerequisite for resistance to obesity. Hopefully they will provide a background for future genetic studies involved in resistance to atherosclerosis.     

Arthritis in a child secondary to congenital insensitivity to pain and self-aggression. Why and when pain is good?

A 9 year-old female child presented with recurrent arthritis of ankles, left knee and unequal leg length. Clinical examination revealed mild valgus deformity in her left knee with grade 2 effusion, arthritis of both ankles and deformity in her left wrist. Examination of the affected joints showed no evidence of tenderness upon active or passive movements and the patient did not show any limping upon gait analysis. Past history of the patient revealed evidence of previous dislocation of her left hip and previous fibular fracture. Revision of her previous x-rays showed left hip dislocation, fracture left fibula and fracture of right metatarsal bone after repetitive trauma which pass unnoticed. Recent x-ray of her left knee showed osteochondral injury. Laboratory investigations were done to rule out common causes of childhood arthritis and revealed: ESR 12 1st hours, CRP negative, negative rheumatoid factor, and negative ANA. Neurological evaluation of the patient documented congenital insensitivity to pain and EMG studies confirmed evidence of sensory neuropathy. Traumatic arthritis resulting from congenital insensitivity to pain with self-aggression is rarely encountered in children but should be considered in the differential diagnosis specially if radiological features point to repetitive trauma with attempts of healing.