A novel mis-sense mutation (G1381A) in the G6PD gene identified in a Chinese man

Objective　To detect new mutations among 29 glucose-6-phosphate dehydrogenase (G6PD) deficient individuals from Yunnan province. Methods　The nitroblue tetrazolium (NBT) method was used to screen G6PD deficient individuals. Mutation was identified by single strand conformation polymorphism (SSCP), amplification created restriction site (ACRS), amplification refractory mutation system (ARMS) and DNA sequencing. Results　Among 29 cases, 18 cases of G1388A, 1 case of C1004A, and 1 case of G1381A were identified. Nine cases remained to be defined. The G1381A mutation is a novel mis-sense mutation, with a substitution of threonine for alanine (A461T). The resultant G6PD had reduced enzymatic activity. In addition, G1381A caused a restriction site of Stu I to disappear, providing a rapid method for the detection of this mutation. Conclusion　A novel mis-sense mutation G1381A was found. This mutation results in a substitution of threonine for alanine, producing enzyme with reduced activity. The loss of the Stu I restriction site offers a rapid method for the detection of this mutation.     

SOX5: Lamb–Shaffer syndrome—A case series further expanding the phenotypic spectrum

To delineate further the clinical phenotype of Lamb–Shaffer Syndrome (LSS) 16 unpublished patients with heterozygous variation in SOX5 were identified either through the UK Decipher database or the study team was contacted by clinicians directly. Clinical phenotyping tables were completed for each patient by their responsible clinical geneticist. Photos and clinical features were compared to assess key phenotypes and genotype–phenotype correlation. We report 16 SOX5 variants all of which meet American College of Medical Genetics/Association for Clinical Genomic Science ACMG/ACGS criteria class IV or V. 7/16 have intragenic deletions of SOX5 and 9/16 have single nucleotide variants (including both truncating and missense variants). The cohort includes two sets of monozygotic twins and parental gonadal mosaicism is noted in one family. This cohort of 16 patients is compared with the 71 previously reported cases and corroborates previous phenotypic findings. As expected, the most common findings include global developmental delay with prominent speech delay, mild to moderate intellectual disability, behavioral abnormalities and sometimes subtle characteristic facial features. We expand in more detail on the behavioral phenotype and observe that there is a greater tendency toward lower growth parameters and microcephaly in patients with single nucleotide variants. This cohort provides further evidence of gonadal mosaicism in SOX5 variants; this should be considered when providing genetic counseling for couples with one affected child and an apparently de novo variant.     

Contraception: Contraception with NORPLANT(R) implants

NORPLANT^® progestogen-only implant contraception providesseveral years of effective protection against pregnancy followinga single application. It is reversible whenever desired, withreturn to normal fertility. Drug release and concentrationsare maximal in the first month of use, when a set of six capsulesreleases 85/µg/day of levonorgestrel. Release is 25–30/µg/dayat 60 months. Circulating drug concentrations and pregnancyrates vary inversely with body weight at placement, but evenamong heavier women, failure rates are below those of oral contraceptivesin the general population. Side-effects are most marked at theinitiation of use. Disruption of normal menstrual patterns occursin 70–80% of recipients initially. Menstrual blood lossis decreased, however, and most women experience modest increasesin haemoglobin. Headache, acne, other skin or hair problems,changes of weight and of mood and abdominal pain, are the mostcommon side-effects attributed to NORPLANT^® contraception.The frequency of occurrence of side-effects diminishes withincreased duration of use. The comparative paucity of majorside-effects, coupled with the method‘s convenience andeffectiveness and its very long action have made NORPLANT^®implants highly acceptable in both developing and developedcountries.     

Use of psychoactive substances in three medical specialties: anaesthesia,medicine and surgery

In order to determine the prevalence of psychoactive substance use in three specialty groupings, 1,624 questionnaires were sent to physicians in medicine, surgery and anaesthesia; all had trained at the same academic institution. A response rate of 57.8% was achieved. Comparison of prevalence of impairment rates showed no differences between Surgery (14.4%), Medicine (19.9%) and Anaesthesia (16.8%). Substance abuse was clearly associated with a family history of abuse; 32.1% of the abusers had a family history of such abuse compared with 11.7% of the non-abusers. Increased stress at various career stages did not appear to increase substance abuse; problem areas during medical life times were similar for each specialty. Substances most frequently used were marijuana (54.7%), amphetamines (32.9%); and benzodiazepines (25.1%). Seventy-three used psychoactive drugs which were non-prescribed. Drug counselling programmes were judged inadequate by most. Use of alcohol and drugs by faculty members was reported by a number of respondents.     

Which nutritional measurements assess protein-energy nutritional status in patients receiving home parenteral nutrition?

Weight, midarm circumference, triceps skinfold thickness, arm muscle circumference, albumin, prealbumin, transferrin and total lymphocyte count were measured at each outpatient visit in patients reveiving home parenteral nutrition from September 1987 to November 1991. Each nutritional variable was analysed for individuals and for the whole group. Group data were expressed using the actual values obtained and successive differences (the change between clinic attendances). Nutritional variables were evaluated using a correlation matrix. Identical analysis of individual and group data demonstrates that laboratory investigations are of little value in the assessment of nutritional status in patients receiving home parenteral nutrition. Anthropometry detected changes in body weight secondary to changes in muscle and/or fat in 80% of patients. Pooling anthropometric data distors the relationship between variables owing to inter-individual variability when actual values are used. The method of successive differences is the preferred method of analysis for group anthropometric data.     

Surface Modification of Poly(lactide-co-glycolide) Nanospheres by Biodegradable Poly(lactide)-Poly(ethylene glycol) Copolymers

The modification of surface properties of biodegradable poly(lactide-co-glycolide) (PLGA) and model polystyrene nanospheres by poly(lactide)-poly(ethlene glycol) (PLA:PEG) copolymers has been assessed using a range of in vitro characterization methods followed by in vivo studies of the nanospheres biodistribution after intravenous injection into rats. Coating polymers with PLA:PEG ratio of 2:5 and 3:4 (PEG chains of 5000 and 2000 Da, respectively) were studied. The results reveal the formation of a PLA: PEG coating layer on the particle surface resulting in an increase in the surface hydrophilicity and decrease in the surface charge of the nanospheres. The effects of addition of electrolyte and changes in pH on stability of the nanosphere dispersions confirm that uncoated particles are electrostatically stabilized, while in the presence of the copolymers, steric repulsions are responsible for the stability. The PLA:PEG coating also prevented albumin adsorption onto the colloid surface. The evidence that this effect was observed for the PLA:PEG 3:4 coated nanospheres may indicate that a poly(ethylene glycol) chain of 2000 Da can provide an effective repulsive barrier to albumin adsorption. The in vivo results reveal that coating of PLGA nanospheres with PLA:PEG copolymers can alter the biodistribution in comparison to uncoated PLGA nanospheres. Coating of the model polystyrene nanospheres with PLA:PEG copolymers resulted in an initial high circulation level, but after 3 hours the organ deposition data showed values similar to uncoated polystyrene spheres. The difference in the biological behaviour of coated PLGA and polystyrene nanospheres may suggest a different stability of the adsorbed layers on these two systems. A similar biodistribution pattern of PLA:PEG 3:4 to PEG 2:5 coated particles may indicate that poly(ethylene glycol) chains in the range of 2000 to 5000 can produce a comparable effect on in vivo behaviour.     

Integrated communications perspectives and the practice of total quality management

Communication is becoming increasingly identified as a significant factor influencing the ability of the NHS to achieve high-quality outcomes. Typically, organizations have tended to conceptualize communication as a process dealing with external relationships. Emphasizes the importance of both internal and external communications, and argues that the NHS now needs to integrate both these dimensions of the communication function. Proposes a strategic framework which suggests how this can be accomplished. Proposes and discusses a communications-centred model of the management process in the light of this approach. This model integrates perspectives which have hitherto dichotomized management as either a science or an art. It also locates communication at the heart of effective management. Finally, suggests the NHS is uniquely well placed to provide data on the impact and costs of total communication programmes.     

Human phase I vaccine trials of 3 recombinant asexual stage malaria antigens with Montanide ISA720 adjuvant

Two phase I vaccine trials were conducted to test the immunogenicity and safety of a vaccine containing three recombinant malaria antigens from the asexual stage of Plasmodium falciparum. The three antigens are a fragment of MSP1 (190LCS.T3); MSP2 and a portion of RESA and were formulated in Montanide ISA720 adjuvant. These trials investigated the dose response of each antigen for eliciting both antibody and T-cell responses and the immunogenicity of a mixture of the antigens compared with the antigens injected separately. All three antigens elicited both antibody and T-cell responses. Strong T-cell responses were observed with 190LCS.T3 and RESA with stimulation indices exceeding 100 for peripheral blood leucocytes in some individuals. The antibody responses were generally weak. The human antibody responses observed with MSP2 in Montanide ISA720 were not significantly different from those obtained in an earlier trial which used MSP2 with alum as the adjuvant. No antigenic competition was observed: volunteers receiving a mixture of antigens had similar responses to those receiving the three antigens at separate sites. Tenderness and pain at the injection site were common over the first few days following immunization. In some volunteers, especially those receiving the highest doses tested, there was a delayed reaction at the injection site with pain and swelling occurring approximately 10 days after injection.