Theoretical calculation of the longitudinal spherical aberration of rigid and soft contact lenses

Although previous investigators have attempted to calculate the longitudinal spherical aberration inherent in soft and rigid contact lenses both on and off the eye, the use of inappropriate assumptions on which to base their calculations has left the problem unresolved. In this study, the longitudinal spherical aberration of both soft and rigid contact lenses was calculated surface by surface both in air and on the eye using a two-dimensional, exact ray tracing program. The erroneous assumptions made by previous investigators were avoided by using an elliptical model for the anterior corneal surface and assuming that the posterior surfaces of soft lenses aligned exactly with the anterior corneal surface after flexure onto the eye. The results demonstrated that, with a 6-mm pupil, contact lenses induce significant levels of spherical aberration in the ocular system for soft lenses of back vertex power greater than +3.00 D or -6.00 D and for rigid lenses of powers more positive than -3.00 D. It is suggested that visual disturbance due to induced spherical aberration has not been a major clinical problem in the past because these conditions fall outside those experienced by a large proportion of the contact lens-wearing public.     

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.     

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.     

The importance of self-examination in the earliest diagnosis of multiple primary cutaneous melanomas: a report of 47 cases

BACKGROUND: Development of more than one primary melanoma in a patient is a relatively uncommon but well-recognized phenomenon. Its frequency has ranged from 1.2% to 8.2% in several series. This subgroup of patients with multiple primary lesions has not been characterized sufficiently. We report the experience of the Melanoma Unit of University Hospital Spedali Civili of Brescia, Italy. METHOD: Study subjects were drawn from 1240 patients with histologically confirmed melanoma, including melanoma in situ. From this group, multiple melanomas developed in 47 patients (3.79%). Every one of our patients has been taught to perform self-examination of the skin to detect suspicious pigmented lesions. RESULTS: Of the 47 patients described in this study, 38 had two primary melanomas, 7 had three melanomas and 2 had 5 and 10 melanomas, respectively. Mean age at first diagnosis was 46.2 years. The majority of subsequent melanomas (74.5%) were removed within 5 years of the initial operation. Synchronous lesions were found in 10 patients. In male patients, the lesion appeared most frequently on the trunk; in female patients, melanoma appeared mostly on the lower extremities. The second primary melanomas developed in the same anatomic region from the first in 53.2% of our patients. The proportion of in situ to invasive melanomas was greater for the second melanomas compared with the first melanomas. Regarding invasive melanomas, the mean thickness of the first melanomas was 1.31 mm compared with 0.66 mm for the second ones. Dividing patients into two groups, of more and less than 50, it is highlighted that in older patients synchronous lesions appear more frequently (36.4% vs. 8.0%); the median time interval between sequential melanomas is longer (84 vs. 63.7 months); and the ratio between the primary and secondary melanoma mean thickness is lower (1.21 : 1.08 vs. 1.43 : 0.63 mm). CONCLUSIONS: The study confirms that second primary melanoma is usually thinner than the first lesion, and it is more common in the same region of the body as the initial melanoma. The highest risk for a second melanoma is during the first 5 years, but a much longer time interval of 28 years is possible. Continued medical follow-up with complete skin examinations seems prudent, but it is very important to promote self-skin evaluation in patients to detect not only metastases but also subsequent primary melanomas in their earliest phases.     

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.