Hypoxia and anaemia in head and neck squamous cell carcinoma – mechanisms of therapy failure and provision of new therapeutic targets

? Head and neck squamous cell carcinoma (HNSCC) represents the sixth most common tumour worldwide. ? Tumour hypoxia and anaemia are both independent prognostic indicators of disease free and overall survival in solid tumours, including HNSCC. ? Hypoxia promotes tumour progression through the hypoxia inducible factor 1 pathway (HIF‐1), upregulating factors that control angiogenesis, glycoloysis, pH regulation, erythropoiesis and apoptosis. ? Oxygen delivery to tumours is influenced by the oxygen carrying capacity of the blood, and therefore anaemia may promote tumour hypoxia. ? Targeting the HIF‐1 pathway and anaemia represent potential therapeutic targets in HNSCC and other solid tumours.     

The relationship between panic attacks and chemical dependencies

The purposes of the present study were to (a) determine the prevalence and characteristics of panic attacks in an alcohol/drug abuse inpatient population, (b) compare patients who reported experiencing panic attacks to patients who have never experienced a panic attack on various self-report measures of psychopathology and on ratings completed by Caregivers, and (c) to examine differences within groups of panickers. One hundred forty-four patients completed the questionnaires over a 17 week period. Over 50% of the patients reported experiencing one or more attacks in the three weeks prior to testing. These panickers scored higher than non-panickers on various measures of psychopathology. Over 83% of panickers reported using alcohol to self-medicate their panic attacks with almost 72% of them believing this procedure to be effective for preventing or reducing panic attacks. Male panickers differed from female panickers on several measures as did panickers who reported their panic attacks began before the alcohol abuse compared to those who did not believe this. The mean history of panic attacks was 103.4 months while the mean history of alcohol abuse was 134.6 months.     

Salvage therapy for prostate cancer recurrence after radiation therapy

Radiotherapy has been successful in treating localized prostate cancer; however, a subset of patients will experience disease recurrence. Determination of the recurrence location must be made using pretreatment and posttreatment clinical variables, imaging, and postradiotherapy biopsy. Patients presumed to have local-only recurrence, optimal clinical risk factors, and an extended life expectancy may be considered for salvage local treatment. Current options include salvage surgery, cryoablation, and brachytherapy. Although they are associated with higher morbidity than primary therapy, salvage treatments can be effective and can still provide patients with a good oncologic and functional outcome. As these modalities continue to improve and patient selection is optimized, better results will evolve.     

CNS 7056: A Novel Ultra-short-acting Benzodiazepine

Background: A new benzodiazepine derivative, CNS 7056, has been developed to permit a superior sedative profile to current agents, i.e., more predictable fast onset, short duration of sedative action, and rapid recovery profile. This goal has been achieved by rendering the compound susceptible to metabolism via esterases. The authors now report on the profile of CNS 7056 in vitro and in vivo.

Methods: The affinity of CNS 7056 and its carboxylic acid metabolite, CNS 7054, for benzodiazepine receptors and their selectivity profiles were evaluated using radioligand binding. The activity of CNS 7056 and midazolam at subtypes ([alpha]1[beta]2[gamma]2, [alpha]2[beta]2[gamma]2, [alpha]3[beta]2[gamma]2, [alpha]5[beta]2[gamma]2) of the [gamma]-aminobutyric acid type A (GABAA) receptor was evaluated using the whole cell patch clamp technique. The activity of CNS 7056 at brain benzodiazepine receptors in vivo was measured in rats using extracellular electrophysiology in the substantia nigra pars reticulata. The sedative profile was measured in rodents using the loss of righting reflex test.

Results: CNS 7056 bound to brain benzodiazepine sites with high affinity. The carboxylic acid metabolite, CNS 7054, showed around 300 times lower affinity. CNS 7056 and CNS 7054 (10 [mu]m) showed no affinity for a range of other receptors. CNS 7056 enhanced GABA currents in cells stably transfected with subtypes of the GABAA receptor. CNS 7056, like midazolam and other classic benzodiazepines, did not show clear selectivity between subtypes of the GABAA receptor. CNS 7056 (intravenous) caused a dose-dependent inhibition of substantia nigra pars reticulata neuronal firing and recovery to baseline firing rates was reached rapidly. CNS 7056 (intravenous) induced loss of the righting reflex in rodents. The duration of loss of righting reflex was short (< 10 min) and was inhibited by pretreatment with flumazenil.     

Disappointing results and low tolerability of photodynamic therapy with topical 5-aminolaevulinic acid in psoriasis. A randomized, double-blind phase I/II study

BACKGROUND: Based on good results in the treatment of superficial skin tumours, since the early 1990s topical photodynamic therapy with aminolaevulinic acid (ALA PDT) has been used for disseminated, inflammatory dermatoses including psoriasis. However, there is still a lack of well-documented trials. OBJECTIVE: A prospective randomized, double-blind phase I/II intrapatient comparison study was conducted in 12 patients to investigate whether topical ALA PDT is an effective treatment for chronic plaque-type psoriasis. METHODS: In each patient three psoriatic plaques were randomly treated with a light dose of 20 J/cm(2) and 0.1%, 1% and 5% ALA, respectively. Treatment was conducted twice a week until complete clearance or for a maximum of 12 irradiations. Therapeutic efficacy was assessed by weekly determination of the psoriasis severity index (PSI). RESULTS: The mean percentage improvement was 37.5%, 45.6% and 51.2% in the 0.1%, 1% and 5% ALA-treated groups, respectively. Irradiation had to be interrupted several times because of severe burning and pain sensation. CONCLUSION: Topical ALA PDT did not prove to be an appropriate treatment option for plaque-type psoriasis due to disappointing clinical efficacy, the time-consuming treatment procedure and its unfavourable adverse event profile.     

Neonatal septicaemia due to non-capsulate Haemophilus influenzae in three siblings.

I report the case of a woman who, in three successive pregnancies, gave birth to premature infants with septicaemia due to non-capsulate Haemophilus influenzae. All three infants displayed characteristic features of the disease. Maternal antenatal and postnatal management is discussed.