INTERVENTION BY AN ALCOHOL HEALTH WORKER IN AN ACCIDENT AND EMERGENCY DEPARTMENT

We have evaluated the effect of brief intervention by an alcoholhealth worker on alcohol consumption by 202 alcohol misusingpatients. For 71 patients where questionnaires were successfullycompleted, 46 (65%) reported drinking less alcohol at 6 monthsas opposed to six (8.5%) who reported drinking more. The overallreduction was statistically significant (P < 0.001), witha mean reduction of 43%.     

A novel functional role for the highly conserved α-subunit KVGFFKR motif distinct from integrin αIIbβ3 activation processes

BACKGROUND: The highly conserved integrin alpha-subunit membrane-proximal motif KVGFFKR plays a decisive role in modulating the activation of integrin alphaIIbbeta3. Previously, we have shown that a platelet permeable palmityl (pal)-peptide with this seven amino acid sequence can directly activate alphaIIbbeta3 leading to platelet aggregation. OBJECTIVES: To investigate further the role of the KVGFFKR motif in integrin alphaIIbbeta3 function. METHODS: We used two sequence-specific complementary model systems, palmityl pal-peptides in platelets, and mutant alphaIIbbeta3-expressing Chinese Hamster Ovary (CHO) cell lines. RESULTS: In platelets we show that the two phenylalanine amino acids in pal-KVGFFKR (pal-FF) peptide are critical for stimulating platelet aggregation. Pal-FF peptide treatment of platelets also gives rise to a tyrosine phosphorylation signal despite the presence of inhibitors of fibrinogen binding. In CHO cells, a double alanine substitution, alphaIIb(F992A, F993A)beta3, induces constitutive integrin activation but prevents actin stress fiber formation upon adhesion to fibrinogen, suggesting that alphaIIbbeta3-mediated cytoskeletal reorganization is also dependent on F992 and F993. This further highlights a critical role for the two phenylalanine residues in both of these alphaIIbbeta3-mediated processes. CONCLUSION: In addition to regulating integrin alphaIIbbeta3 activation state, the KVGFFKR motif also influences cytoskeletal reorganization. This activity is critically determined by F992 and F993 within the seven amino acid sequence.     

Assessment of cognitive and adaptive behaviour among individuals with congenital insensitivity to pain and anhidrosis

Aim Individuals with congenital insensitivity to pain with anhidrosis (CIPA) are reported to have mental retardation* but to our knowledge no detailed study on the subject has ever been published. The present study assessed and documented cognitive and adaptive behaviour among Arab Bedouin children with CIPA. Methods Twenty‐three Arab Bedouin children (12 females, 11 males) with CIPA aged between 3 and 17 years (mean 9y 7mo, SD 4y 2mo) were assessed. They were compared with 19 healthy siblings of the affected children aged between 5 and 13 years (mean 8y 11mo, SD 2y 10m). All of the children in the comparison group, but only half of the CIPA group, were attending school. The children were evaluated using a standardized, non‐verbal intelligence test, the Leiter International Performance Scale – Revised, and an adaptive behaviour questionnaire, the Vineland Adaptive Behaviour Scales, 2nd edition. Results Based on scores on the intelligence test and the adaptive behaviour scale, children with CIPA functioned in the mental retardation range (mean IQ scores: CIPA group 53.8, comparison group 83.32 [p<0.001]; adaptive behaviour: CIPA group 68.1, comparison group 104.88 [p<0.001]). IQ was significantly higher among the children with CIPA aged up to 7 years 11 months than among the older children 73.83 vs 45.21 (p<0.001). Interpretation As a group, the younger children with CIPA may be functioning above the mental retardation range. We propose that early intervention addressing these children’s needs and developing an appropriate educational system, might improve their outcome.     

A 14-Week Vapor Inhalation Toxicity Study of Methyl Isobutyl Ketone

In a 2-week probe study male and female Fischer- 344 rats andB6C3F1 mice were exposed 6 hr/day to 2000, 500, 100, or 0 ppmmethyl isobutyl ketone (MIBK). At 2000 ppm there was a slightincrease in male rat liver weight (absolute and relative). Theonly changes observed histologically were increases in regenerativetubular epithelia and hyalin droplets in kidneys of male ratsexposed to 2000 or 500 ppm. Exposure levels for a subchronicstudy were 0, 50, 250, or 1000 ppm methyl isobutyl ketone vapors6 hr/day, 5 days per week, for 14 weeks. The 14 weeks of exposurehad no adverse effect on the clinical health or growth of ratsor mice. Male rats and male mice exposed to 1000 ppm MIBK hada slight but statistically significant increase in liver weightand the liver weight/body weight ratio. Liver weight was alsoincreased slightly in male mice exposed to 250 ppm. No grossor microscopic hepatic lesions related to MIBK exposure wereobserved. Furthermore, the only microscopic change observedwas an increase in the incidence and extent of hyahin dropletswithin proximal tubular cells of the kidneys of male rats exposedto 250 and 1000 ppm of MIBK. The relevance of the male rat kidneytubular effect to humans is not known. In conclusion, otherthan the male rat kidney effect, exposure of male and femalerats and mice to MIBK at levels up to 1000 ppm for 14 weekswas without significant toxicological effect.     

Thymic carcinosarcoma associated with a spindle cell thymoma: an immunohistochemical study

A case of thymic carcinosarcoma associated with a spindle cell thymoma in a 71-year-old woman is reported. Histological and immunohistochemical studies of the carcinosarcoma showed two quite different components: the sarcomatous component included cells with myoid differentiation which stained for desmin and muscle specific actin, and some isolated cells which stained positively for low molecular weight cytokeratin, while the carcinomatous component, which formed less than 10% of the tumour, showed an epithelial phenotype, being positive for low and high molecular weight cytokeratin and epithelial membrane antigen. The thymoma cells showed epithelial markers, and a few cells were also positive for desmin and muscle specific actin. The rarity of this tumour and its possible histogenesis are discussed.     

Clinical utility of fluorometric scanning of plasma porphyrins for the diagnosis and typing of porphyrias

The fluorometric emission scanning (using excitation at 405 nm) of plasma samples, simply diluted five-fold in phosphate-buffered saline, allows the differentiation of three conditions according to their porphyrin content. The emission maximum at 626–628 nm is a specific finding in variegate porphyria, while in erythropoietic protoporphyria a characteristic peak is found at 636 nm. A fluorescence emission maximum at 618–622 nm corresponds to a third group that includes normal subjects, non-porphyria patients and patients suffering from acute intermittent porphyria, hereditary coproporphyria, congenital erythropoietic porphyria (Günther disease) and porphyria cutanea tarda. Therefore, this simple, quick and cheap screening test allows one to establish whether a patient with a photocutaneous syndrome has porphyria and whether this porphyria belongs to the types: variegate, protoporphyria or other cutaneous porphyrias.