Psychosocial aspects and perspectives of adult-onset type 1 diabetes: A systematic scoping review.

AIM: To map existing research on psychosocial aspects of adult-onset type 1 diabetes (T1D), including psychosocial health status, ways psychosocial aspects may affect management of T1D in everyday life, and interventions targeting management of adult-onset T1D. METHODS: We conducted a systematic search in MEDLINE, EMBASE, CINAHL and PsycInfo. Search results were screened with predefined eligibility criteria, followed by data extraction of the included studies. Charted data were summarized in narrative and tabular form. RESULTS: We included 10 reports describing nine studies from the 7302 identified in the search. All studies were conducted in Europe. Participant characteristics were missing in several studies. Five of the nine studies incorporated psychosocial aspects as the main aim of the study. Limited information on psychosocial aspects was available in the remaining studies. We identified three overarching themes related to psychosocial aspects: (1) the impact of the diagnosis on everyday life, (2) the influence of psychosocial health on metabolic levels and adaptation, and (3) provision of self-management support. CONCLUSIONS: Research focussing on psychosocial aspects of the adult-onset population is scarce. Future research should involve participants across the adult life age span and from a wider geographical area. Sociodemographic information should be collected to explore different perspectives. Further exploration of suitable outcome measures considering adults' limited experience of living with the condition is needed. This would help to better understand how psychosocial aspects may affect management of T1D in everyday life and thus enable healthcare professionals to provide appropriate support to adults with new-onset T1D.

Anti-Müllerian hormone, a Sertoli cell-derived marker, is decreased in plasma of male patients in all stages of chronic kidney disease.

Male patients with terminal renal failure are often infertile and exhibit an abnormal sex hormone pattern in plasma. We studied patients in all chronic kidney disease (CKD) stages to determine plasma levels of anti-Müllerian hormone (AMH), a Sertoli cell-derived marker, and other sex hormones. Seventy-eight male patients with CKD stages 1-5 and a median age of 40 years (22-50 years), as well as 20 healthy controls with a median age of 37 years (26-44 years), were enrolled. The CKD patients were evenly distributed; 18 with CKD stages 1-2, 19 with CKD stage 3, 19 with CKD stage 4, and 22 with CKD stage 5. Cystatin C, follicle-stimulating hormone, luteinizing hormone, prolactin, sex hormone-binding globulin, testosterone, and AMH levels in plasma were analysed. AMH was analysed using the Ansh Labs UltraSensitive AMH assay. Several changes occurred in plasma levels of sex hormones in male patients with CKD. Plasma AMH levels were lower in CKD stages 1-4 by 30% (p = 0.041) and by 70% (p < 0.001) in CKD stage 5 compared with controls. Plasma luteinizing hormone and prolactin levels were higher and testosterone levels were lower compared with controls. The pathophysiological role of this reduction in AMH is unclear, but can be linked to altered Sertoli cell function.

Linezolid as rescue treatment for left-sided infective endocarditis: an observational, retrospective, multicenter study.

The increasing number of resistant bacterial strains in infective endocarditis (IE) emphasizes the need for a constant development of antimicrobials. Linezolid is an oxazolidinone with an effect on Gram-positive cocci. Only a few casuistic reports describe its utilization in the treatment of IE. The objective of this study is to report our experience with linezolid from a large consecutive cohort of IE patients. In a retrospective cohort study, data on 550 consecutive IE patients were collected at two tertiary University Hospitals in Copenhagen, Denmark. The main endpoints were differences in the in-hospital and 12 months post-discharge mortality between IE patients receiving linezolid for a part of the treatment and IE patients receiving conventional treatment. Of the 550 patients enrolled in the study, 38 patients received linezolid treatment and 512 received conventional treatment. Reasons for adding linezolid were antibiotic intolerance (n = 13), nephrotoxicity (n = 5), pharmaceutical interactions (n = 1), inadequate clinical response (n = 14), or inadequate microbial response (n = 5). No significant differences in the cure rate (74 % vs. 71 %, p > 0.05), in-hospital mortality (13 % vs. 14 %, p > 0.05), or post-discharge mortality at 12 months follow-up (26 % vs. 26 %, p > 0.05) were observed. In the current study, we found that linezolid, in general, was well tolerated and associated with the same outcome as in patients with Gram-positive IE treated with other antibiotics.

A quantitative enzyme-linked immunoassay for the detection of 2, 6-dichlorobenzamide (BAM), a degradation product of the herbicide dichlobenil.

2,6-Dichlorobenzamide (BAM) is the dominant degradation product in soil of the widely used herbicide dichlobenil. To detect BAM in water, a highly sensitive and specific enzyme-linked immunosorbent assay (ELISA) was developed. As an alternative to conventional coating of ELISA plates, the assay is based on direct covalent immobilisation. We achieved a surface which requires a short time for the immobilisation of ligand, is stable under dry storage, and which permits assays with a low CV. The performance of the assay was demonstrated by an inter-well CV that was generally less than 6%, a detection limit (DL(15)) of 0.02 microg/l and an IC(50) of 0.19 microg/l. Cross-reactivity was measured against nine analytes with structural homology to BAM. The highest degree of cross-reactivity (10.8%) was seen with 2,6-dichlorothiobenzamide (Chlorthiamid). Considering an EU-limit of 0.1 microg/l as the permissible maximum for the presence of pesticides in drinking water, this ELISA-procedure is suitable for large-scale screening of water samples suspected of being contaminated with BAM.

Transmission of a minor variant of transcriptionally active HIV-1.

We investigated the genotypic variation of pro-viral human immunodeficiency virus type 1 (HIV-1) DNA in a virus donor-recipient pair by comparing sequences from the HIV-1 V3 region of the gp120 gene and the p17gag gene. We found that the transmitted virus was a minor variant in the donor's virus population in blood. Possible selection mechanisms within the host (neutralization by antibodies) were studied in order to investigate whether antibodies could explain the conserved HIV genotype found in the recipient. In conclusion, our data indicate that a minor variant of pro-viral transcriptionally active HIV-1 found in PBMC was transmitted from donor to recipient. Development of a homogeneous genotype regarding the V3 region (V3d-B1(1)) of pro-viral DNA in the recipient's PBMC and a partially homogeneous genotype regarding the HIV-RNA was possibly caused by an envelope associated selection that is not dependent upon neutralizing antibodies.

Prevalence of malnutrition in surgical patients: evaluation of nutritional support and documentation.

OBJECTIVES: To assess the nutritional status of surgical gastrointestinal and orthopaedic patients, and to audit the practice and documentation of nutritional therapy used on these wards. METHODS: Nutritional status was assessed in 244 patients using body mass index (BMI) and weight loss. Amount and length of nutritional therapy and records of the patients' nutritional state were noted from the patients' records. RESULTS: 94 patients (39%) were mildly/borderline to severely malnourished. Sixty courses of nutritional support were given parenterally or by tube feeding. Twenty seven of these were given for less than a week. Of the remaining 33, the amount of energy given to 17 patients was less than 25 kcal/kg. There was no correlation between patient weight and energy administered. Twenty four patients received less than 1 gram aminoacids per kg bodyweight. Body weight was recorded in 59% of the patients records. CONCLUSION: New routines and staff education are needed.

Reactions of N-N and N-O compounds with horseradish peroxidase and peroxidases from Mycobacterium tuberculosis.

Several N-N-and N-O-containing compounds were analysed for their ability to act as substrates for horseradish peroxidase and peroxidases in Mycobacterium tuberculosis extracts. Aminoguanidine, diaminoguanidine, isoniazid, hydroxylamine and hydrazine were found to be weak substrates for horseradish peroxidase in reaction I and to inhibit the reaction of horseradish peroxidase with hydrogen peroxide. The same compounds inhibited the reaction of Mycobacterium tuberculosis peroxidase-catalase with hydrogen peroxide, and hydroxylamine was found to be a weak substrate for this enzyme. In growth inhibition experiments, diaminoguanidine inhibited the growth of M. tuberculosis H37Rv at 50 microg/mL, but not the growth of two isoniazid-resistant strains. Isonicotinic acid hydroxamate inhibited the reaction of the peroxidases with hydrogen peroxide, but was not itself a substrate and had no growth-inhibitory effects. On the basis of these results we suggest that the effect of isoniazid on growth of M. tuberculosis results from increased oxidative stress due to inhibition of catalase-peroxidase as well as from generation of toxic radicals with the structure [structure in text].

Comparisons of DNA-mediated immunization procedures directed against surface glycoproteins of human immunodeficiency virus type-1 and hepatitis B virus.

DNA vaccination methods were compared to examine the in vivo expression of HIV-1 gp160 and beta-galactosidase, and the resulting immune response. Beta-galactosidase plasmid showed expression rates of 2-5% of muscle fibers with or without pretreatments using bupivacaine or cardiotoxin facilitators 1 or 5 days earlier, respectively. In contrast, HIV gp160 expression was lower in untreated or bupivacaine-treated muscles, but was improved by pretreatment with cardiotoxin. Equal expression of beta-galactosidase and HIV gp160 was obtained using gene gun delivery to the epidermis. Unlike the i.m. in situ expression of gp160, the anti-HIV antibody response did not improve after muscle pretreatments but depended on the vaccination intervals. Gene gun delivery of pMN160 also resulted in a slow and low titered antibody response. In contrast, a single i.m. injection of plasmid encoding another viral envelope, HBsAg, resulted in earlier seroconversion to high titers without the need for pretreatments or boostings. Intradermal inoculation by gene gun using 100-fold less DNA resulted in the same anti-HBsAg antibody profile only after boostings. In contrast to the differences in antibody responses, a specific CTL response was obtained in all cases. Bupivacaine-treated muscles showed an extreme degree of edema with disruption of connective tissue (endo- and mesomysium) and was not well tolerated (4 of 19 mice died). Cardiotoxin created muscle necrosis and occasional (2 of 20 mice) development of fibrotic muscles. It is concluded that in vivo expression cannot be properly predicted using reporter gene experiments and that the resulting immune response does not follow directly with the expression rate. It is suggested that the antibody response may depend primarily on the nature of the antigen expressed rather than the DNA vaccination method. It is proposed that gene gun or i.m. injection be used without pretreatment in the case of DNA vaccination with plasmid encoding HIV MN gp160.

Polyamine-stimulated binding of diamine oxidase to DNA.

Diamine oxidase is a Cu-containing enzyme which intracellularly participates in the regulation of the levels of putrescine, spermidine and spermine and in this process produces growth inhibitory amino aldehydes and hydrogen peroxide. Extracellularly, the enzyme participates in the inactivation of biogenic amines, notably histamine. Here we present evidence that in the presence of polyamines, diamine oxidase has the ability to bind DNA and to oxidise DNA-bound polyamines. The enzyme associates with chromosomal DNA since it can be released from human placental DNA by treatment with DNase I and it may be involved in the degradation of DNA. Thus, diamine oxidase may belong to a new class of DNA-binding proteins.

Improved humoral and cellular immune responses against the gp120 V3 loop of HIV-1 following genetic immunization with a chimeric DNA vaccine encoding the V3 inserted into the hepatitis B surface antigen.

The gp120-derived V3 loop of HIV-1 is involved in co-receptor interaction, it guides cell tropism, and contains an epitope for antibody neutralization. Thus, HIV-1 V3 is an attractive vaccine candidate. The V3 of the MN strain (MN V3) contains both B- and T-cell epitopes, including a known mouse H-2d-restricted cytotoxic T lymphocyte (CTL) epitope. In an attempt to improve the immunogenicity of V3 in DNA vaccines, a plasmid expressing MN V3 as a fusion protein with the highly immunogenic middle (pre-S2 + S) surface antigen of hepatitis B virus (HBsAg) was constructed. Epidermal inoculation by gene gun was used for genetic immunization in a mouse model. Antibody and CTL responses to MN V3 and HBsAg were measured and compared with the immune responses obtained after vaccination with plasmids encoding the complete HIV-1 MN gp160 and HBsAg (pre-S2 + S), respectively. DNA vaccination with the HIV MN gp160 envelope plasmid induced a slow and low titred anti-MN V3 antibody response at 12 weeks post-inoculation (p.i.) and a late appearing (7 weeks), weak and variable CTL response. In contrast, DNA vaccination with the HBsAg-encoding plasmid induced a rapid and high titred anti-HBsAg antibody response and a uniform strong anti-HBs CTL response already 1 week p.i. in all mice. DNA vaccination with the chimeric MN V3/HBsAg plasmid elicited humoral responses against both viruses within 3-6 weeks which peaked at 6-12 weeks and remained stable for at least 25 weeks. In addition, specific CTL responses were induced in all mice against both MN V3 and HBsAg already within the first 3 weeks, lasting at least 11 weeks. Thus, HBsAg acts as a 'genetic vaccine adjuvant' augmenting and accelerating the cellular and humoral immune response against the inserted MN V3 loop. Such chimeric HIV-HBsAg plasmid constructs may be useful in DNA immunizations as a 'carrier' of protein regions or minimal epitopes which are less exposed or poorly immunogenic.

Combined immunostaining and Coomassie Brilliant Blue staining of polyvinylidene difluoride membranes without organic solvent.

A method for staining proteins on polyvinylidene difluoride membranes without using organic solvent is described. The method uses preblocking of the membrane with either Tween 20 or polyethylene glycol followed by staining with 0.01% Coomassie Brilliant Blue. No destaining of the membrane is needed afterwards. Preblocking with polyethylene glycol is compatible with microsequencing while Tween 20 leads to very low initial yields. Preblocking with Tween 20 has the additional advantage of allowing immunostaining followed by Coomassie Brilliant Blue staining for total protein on the same membrane.

Quantification of HIV-1 RNA during antiretroviral therapy: association with viral phenotype and development of resistance.

The aim of this study was to analyse the interplay between the treatment responses, as assessed by serum HIV-1 RNA levels and CD4 cell counts, virological phenotype and the development of phenotypic and genotypic resistance. A total of 47 late-stage, HIV-1-infected, antiretroviral-naive patients treated with reverse transcriptase inhibitors (zidovudine or didanosine monotherapy or alternating zidovudine and didanosine) as part of a randomized study and remaining on treatment for a minimum of 1 year were included in the study. Baseline serum HIV-1 RNA levels did not differ between the patients harbouring syncytium-inducing (SI) virus and those harbouring non-syncytium-inducing (NSI) virus (P = 0.66), despite the fact that the group of patients with SI virus had a significantly lower median CD4 cell count (P < 0.00005) and a higher proportion of patients diagnosed with AIDS at study entry (11/19 versus 6/25) than did the group with NSI virus. The patients harbouring SI virus had significantly faster clinical progression than that of the patients harbouring NSI virus (P < 0.001). The patients wit

Development of resistance of zidovudine (ZDV) and didanosine (ddI) in HIV from patients in ZDV, ddI and alternating ZDV/ddI therapy.

OBJECTIVE: To study development of phenotypic and genotypic resistance against zidovudine (ZDV) and didanosine (ddI) during 24 months of mono- and monthly alternating therapy. PATIENTS: Forty-six patients, not previously treated with antiretroviral drugs, were included in the study. METHODS: ZDV and ddI sensitivity were determined in a biological assay based on production of HIV antigen in cultures of CD4+ lymphocytes. The ZDV-associated mutations at codon 41 and 215, and the ddI-associated mutation at codon 74 of the reverse transcriptase (RT) gene were analysed using selective polymerase chain reaction on DNA from peripheral blood mononuclear cells. The biological phenotype [syncytium-inducing (SI)/non-SI(NSI)] of the viral isolates was assessed using a MT2 assay. RESULTS: Of the patients, 82% in ZDV therapy and 73% in alternating therapy developed phenotypic resistant HIV [median inhibitory concentration (IC50) > 0.1 microM]. Patients treated for 1 year with ddI (monotherapy or alternating) had significant higher ddI IC50 values than patients in ZDV monotherapy. During ZDV and alternating therapy, 67 and 75% of the patients, respectively, developed mutations in RT codon 41, whereas 83 and 75%, respectively, developed mutations in codon 215. In patients treated with ddI, 60% developed mutations in codon 74, whereas none of the patients in either alternating ZDV/ddI or ZDV therapy developed this mutation. Forty-six per cent of the patients had SI HIV at start of therapy. Four patients switched from SI to NSI during either ZDV, ddI or alternating therapy. Faster development of resistance was associated with the SI phenotype. CONCLUSIONS: No difference in either phenotypic ZDV or ddI resistance, or genotypic ZDV resistance could be demonstrated during monotherapy or monthly alternating ZDV/ddI therapy, whereas genotypic ddI resistance (mutation in RT codon 74) only were detected in patients in ddI monotherapy. In addition, we found that development of phenotypic and genotypic resistance was faster in patients harbouring SI isolates, and that switches from SI to NSI during therapy was independent of the type of therapy.

In situ detection of diamine oxidase activity using enhanced chemiluminescence.

In need of a simple and sensitive method for detection of diamine oxidase (EC 1.4.3.6) activity in connection with diamine oxidase purification from human placenta, we have developed an enhanced chemiluminescence method using putrescine as substrate and horseradish peroxidase and luminol for the detection of the H2O2 produced by diamine oxidase. The method allows direct detection of small amounts of diamine oxidase in serum samples after agarose gel electrophoresis and allows visualization of diamine oxidase activity in tissue sections. Employing this method we have detected diamine oxidase in sera from cow, horse, monkey, rabbit, and pregnant women. On tissue sections from term human placenta diamine oxidase activity was exclusively localized to the maternal side and was concentrated in vessels and fibrinoid areas.

Periodic deposition of arabinogalactan epitopes in the cell wall of pollen tubes of Nicotiana tabacum L.

The monoclonal antibodies MAC 207 and JIM 8, recognizing arabinogalactan epitopes, were used to localize the corresponding antigenic sites in pollen tubes of Nicotiana tabacum L. grown in vitro or semi in vivo. The analysis of the immunofluorescence labelling was performed by means of confocal laser scanning microscopy. Most pollen tubes were labelled along their length, with the exception of the tip region, in a ring-like pattern with remarkable periodicity. The diameter of the rings was approx. 12 µm and the distance between two rings was about 6 µm. No labelling of the cytoplasm, the vegetative nucleus or the generative cell was observed. The presence of labelling in the non-apical tube wall after pectinase and cellulase digestion indicates that the epitopes for MAC 207 and JIM 8 are located in the inner callosic sheath of the pollen-tube wall.

Isolation and characterization of a soluble antigen complex of Plasmodium falciparum with pyrogenic properties.

A soluble antigen complex, previously designated antigen no. 7 (Ag7) on the basis of the pattern obtained by crossed immunoelectrophoresis of culture supernatants of P. falciparum, was isolated by affinity chromatography. It was shown to be synthesized at the schizont stage of the parasite growth cycle and to be located on the surface of the schizonts. Antibodies to Ag7 did not inhibit the growth of the parasite in vitro. Ag7 is recognized by immune human sera from many parts of the world and it stimulated the production of specific antibody in mice when incorporated into immune-stimulating complex (ISCOM) structures. It also specifically stimulated in vitro proliferation of lymphocytes from clinically immune adults. That it induced the secretion of interleukin 1 by human monocytes and was pyrogenic in rabbits was of particular interest. Thus Ag7 has endotoxin-like properties which make it a possible candidate for an antitoxic malaria vaccine.

Medical social work in the burns unit.

This paper presents the social problem resolving processes in a burns unit integrated in the general hospital service in a welfare society. The social work opens possibilities of improving both patient relationships and society relationships.

Interferon in rabbit sera after inoculation with Treponema pallidum suspensions contaminated with PED virus.

Paired rabbits sera were examined for the presence of interferon and pathogenicity for rabbits. The sera were obtained before and 48 hours after inoculation with Treponema pallidum suspensions of rabbit origin in 12 selected laboratories. Classical interferon, detectable in dilutions from 1/9 to 1/81, were found in 27 out of 39 postinoculation sera from which the pleural effusion disease (PED) virus was isolated. Serum interferon was not detectable in dilutions greater than or equal to 1/9 in 16 virus-negative postinoculation sera or in any of the 55 preinoculation sera. Interferon was found more often in sera from which highly virulent strains of PED virus were isolated than in sera from which strains of low virulence were isolated. The serum interferon assay provides useful presumptive evidence of contamination of rabbit-passaged treponemes with PED virus, but the assay is least useful when PED virus is present subclinically.