Cyclodextrin formulation of dorzolamide and its distribution in the eye after topical administration.

Due to limited aqueous solubility of dorzolamide at physiologic pH, the pH of Trusopt eye drops (cont. 2% dorzolamide) has to be kept at about 5.65, and to increase the topical bioavailability of the drug from Trusopt the contact time of the drug with the eye surface is increased by increasing the viscosity of the eye drops to 100 cps. This low pH and high viscosity can lead to local irritation. In this study, dorzolamide hydrochloride was formulated as 2% and 4% low viscosity solutions (viscosity 3 to 5 cps) containing randomly methylated beta-cyclodextrin at pH 7.45. These formulations were evaluated in rabbits. The animals were sacrificed at various time points after topical administration of the drug and the dorzolamide concentration determined in the different parts of the eye. Trusopt was used as a reference standard. The topical availability of dorzolamide from the cyclodextrin-containing eye drops appeared to be comparable to that from Trusopt and the drug reached retina and optic nerve to give measurable concentrations for at least 8 h after administration of the eye drops.     

Behavioural, physiological and immunological consequences of social status and aggression in chronically coexisting resident-intruder dyads of male rats

The behavioural and physiological consequences of social status and reciprocal fighting in resident-intruder dyads of Long Evans male rats were evaluated. Before a chronic cohabitation of 10 days, residents and intruders were individually housed for one month to increase their aggressiveness. Control animals included isolates, i.e., animals kept individually housed throughout the experiment and pair-housed rats, i.e., pairs of rats housed together from their rats in the laboratory. In 19 out of 20 dyads, a clear dominance relationship developed with an advantage to the resident in 68% of the cases. Dominants showed more exploratory activity than subordinates in a open-field test at the end of the cohabitation period; subordinates groomed longer than animals from other experimental groups. Dominants had lower pain thresholds than individually and pair-housed animals. Both dominants and subordinates had higher tyrosine hydroxylase enzymatic activities in the left adrenal than isolated and pair-housed rats. Subordinates lost body weight and had higher plasma corticosteroid concentrations than animals from the other experimental groups. In addition, they had smaller thymus glands and reduced spleen lymphocyte responses to mitogenic stimulation in vitro, in comparison to dominant animals. These results show that subordination in the dyadic resident-intruder paradigm leads to a complex syndrome of behavioural and physiological changes, some of which may be modulated by the intensity of aggressive interactions.     

Gallibacterium anatis-secreted metalloproteases degrade chicken IgG.

Gallibacterium anatis (previously named Pasteurella haemolytica-like) is considered a normal inhabitant of genital and upper respiratory tracts of healthy chickens, but it is also associated with different pathological conditions. Secreted metalloproteases from field and reference G. anatis cultures were obtained by methanol precipitation and were characterized. Proteins of molecular mass higher than 100 kDa showing proteolytic activity were observed in 10% polyacrylamide gels copolymerized with 1% bovine casein. They were active at alkaline pH, and inhibited by ethylenediamine tetraacetic acid. Their activity was stable at 50 degrees C, but partially inhibited at 60 degrees C, and totally inhibited at higher temperatures. Secreted proteins were able to degrade chicken IgG after 24 h of incubation, and cross-reacted with a polyclonal antibody against purified protease from Actinobacillus pleuropneumoniae. Secreted metalloproteases could play a role in infections caused by G. anatis.     

On the natural course of oral lichen lesions in a Swedish population-based sample

OBJECTIVES: The aim was to assess the natural course of oral lichen lesions (OLL) among unselected, non-consulting individuals. SUBJECTS AND METHODS: A cohort of 327 subjects with OLL, confirmed in 1973-1974 during a population-based survey in two Swedish municipalities, was followed through January 2002 via record linkages with nationwide and essentially complete registers. A sample of 80 drawn from the 194 surviving subjects who still resided in the area in 1993-1995 was invited for interview and oral re-examination. RESULTS: At the end of follow-up, one case of oral cancer was detected, while 0.4 were expected. The overall mortality among subjects with OLL was not significantly different from that in the 15,817 OLL-free subjects who participated in the initial population based survey in 1973-1974. The lesion had disappeared in 14 (39%) of 36 re-examined subjects with white OLLs in 1973-1974, and four (11%) had transformed into red types. In the corresponding group of 19 with red forms initially, five (26%) had become lesion free and four (21%) had switched to white types. Although the cohort size does not permit firm conclusions regarding oral cancer risk, the natural course over up to 30 years appears to be benign in the great majority.     

Changes in immune regulation in response to examination stress in atopic and healthy individuals

BACKGROUND: Stress can aggravate the allergic inflammation, but determinants of disturbed immune regulation are largely unknown. OBJECTIVE: To determine systemic immunological, local inflammatory and functional airway responses to stress in healthy and atopic individuals. METHODS: Forty-one undergraduate students, 22 with allergy of whom 16 had asthma, and 19 healthy controls, were studied in a low-stress period and in association with a large exam. Subjects completed questionnaires on stress and health behaviours, underwent lung function tests, bronchial methacholine challenge, measurements of exhaled nitric oxide and urine cortisol. Blood cells were phenotyped, and cytokines from mononuclear blood cells were analysed. RESULTS: Perceived stress and anxiety increased in both groups during the exam period while cortisol increased only in the atopy group. Cytokine production decreased broadly in response to stress in both groups, which was paralleled by an increase in the proportion of regulatory T cells (CD4(+)CD45RO(+)CD25(bright)). Interestingly, atopic individuals, but not controls, reacted with a decreased T-helper type 1/T-helper type 2 (Th1/Th2) ratio and a decrease in natural killer (NK) cell numbers in response to stress. In control subjects only, exhaled nitric oxide decreased and forced expiratory volume in one second increased during stress. CONCLUSION: Atopic and non-atopic subjects shared some immune changes in response to stress, such as a dramatic decline in cytokines and an increase in the number of regulatory T cells in peripheral blood. However, other stress-induced immune changes were unique to atopic individuals, such as a skewed Th1/Th2 ratio and reduced NK cell numbers, indicating that some pathogenic mechanisms in atopics may be more strongly affected by stress than others.     

Maximized combined modality treatment of an unselected population of oral and oropharyngeal cancer patients. Final results of a pilot study compared with a treatment-dependent prognosis index.

BACKGROUND: In an attempt to raise the survival of an unselected and representative population of oral and oropharyngeal squamous cell cancer patients, a pilot study of an integrated four-modality treatment was conceived. Final endpoints were compliance, loco-regional control, survival (after complete 5-year follow-up), and a concept of trial assessment using the treatment-dependent prognostic index TPI. PATIENTS: Eighty-seven consecutive patients with histologically proven untreated stages I-IV disease presented in the period between 1997 and 1999 of whom 14 had to be considered uncurable and 73 were fit to be treated with the intention of achieving a cure. METHODS: All patients received one cycle of neoadjuvant intraarterial chemotherapy with 150 mg/m(2) cisplatin (systemically neutralized with sodium thiosulphate), and, if possible, by consecutive treatment applying both surgery of the primary tumour and the neck lymphatics, as well as by adjuvant radiation over 5 weeks (51.3 Gy) plus concurrent chemotherapy (weekly systemic docetaxel 25 mg/m(2)). RESULTS: Ninety per cent of all cases and 96% of the patients treated with curative intention received more than one modality due to study design. Patient non-compliance in the group treated with curative intention has been 18/73 (=25%), and protocol compliance has been 32/73 (=44%). The locoregional control rate for all cases was 71% (62/87 patients) and for the patients treated with curative intention 83.5% (61/73 patients). Thirteen/fourteen non-curable patients died after a mean period of 4 months. After a median observation time of 5 years, the final absolute survival of the unselected population was 53%, and of the patients treated with curative intention 62% (especially, 70% and 50% for patients with operable stages III and IV, respectively). CONCLUSION: The multimodality regimen as presented proved feasible and showed high objective and relative survival rates in comparison with known data from tumour registries of unselected populations. Intra-arterial chemotherapy should be considered a valuable addition to treatment. The potential of survival benefit from this multimodality regimen in comparison with the prognosis index TPI should be investigated in further studies.     

A Spanish version of the Family Assessment Device

Introduction  

This paper presents the results of a study on the psychometric properties of an authorized Spanish version of the McMaster Family Assessment Device, a self-report measure of family functioning.     

Benign infantile seizures with mild gastroenteritis: Study of 22 patients

PurposeTo analyze the electroclinical features, aetiology and outcome in patients with normal neurological examination and psychomotor development who presented seizures during a mild gastroenteritis (MG).Patients and methodsEvaluation of the clinical charts of 22 patients who were assessed in the Neurology Department, Hospital Nacional de Pediatría Prof. Dr. JP Garrahan between 1999 and 2007.ResultsTwelve patients were boys and 10 were girls, the age of onset ranged from 5 to 26 months, and the median age was 10 months. Rotavirus antigen test in stool was positive in 9 of 18 studied patients. The seizures were brief, focal with secondary generalization in 15 patients (68.5%), apparently generalized in 5 (22.5%) and focal in two (9%). Seven of the patients (35%) had more than one seizure in 24 h. The interictal EEG was normal in all patients. Neuroradiological studies were performed in 19 patients with a normal result. No patient was put on long-term treatment with antiepileptic drugs. Four patients had subsequent mild gastroenteritis and two of them presented convulsions during the disease. After between 12 and 67 months of follow-up, all patients had normal psychomotor development and neurological examination.ConclusionsIn this study we confirmed the association of benign infantile seizures (BIS) and MG with or without rotavirus. The identification of this entity allows avoiding unnecessary complementary studies and treatment with antiepileptic drugs.