Action myoclonus-renal failure syndrome: a cause for worsening tremor in young adults.
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Adult↗
Biomedical subjects
A Hughes
Publications and source records attributed to A Hughes.
Candida glabrata prosthetic valve endocarditis treated successfully with fluconazole plus caspofungin without surgery: a case report and literature review.
Reported here is the case of a 72-year-old man who was diagnosed with Candida glabrata prosthetic mitral valve endocarditis and treated successfully with fluconazole plus caspofungin after he refused and was determined unfit for surgery. Initial treatment with intravenous amphotericin B resulted in acute renal impairment. Despite 8 days of intravenous fluconazole therapy, he remained fungemic. Caspofungin was added to the treatment regimen with subsequent sterilisation of blood culture. The patient was treated for 34 days with caspofungin and 41 days with fluconazole. He continued oral fluconazole after hospital discharge and remained well at follow-up 11 months later. The role of fluconazole and caspofungin in the treatment of Candida endocarditis is discussed.
Acute Kidney Injury↗
Nutrition support improves patient outcomes, treatment tolerance and admission characteristics in oesophageal cancer.
AIMS: Patients with oesophageal cancer undergoing chemoradiation with curative intent are at high risk of malnutrition and its complications, including increased side effects of treatment. We have developed a nutrition pathway (NP), involving the early then periodic nutrition assessment of all patients presenting to the multidisciplinary oesophageal clinic who were planned to receive definitive chemoradiation. MATERIALS AND METHODS: Patients were assessed as at 'low', 'moderate' or 'severe' nutrition risk, and were provided with appropriate nutrition intervention ranging from preventative advice (low risk), oral nutrition support (moderate risk) to enteral feeding (severe risk). Outcomes for 24 patients treated before implementation of the NP were compared with those of 24 patients treated using the NP. RESULTS: Patients managed using the NP experienced less weight loss (mean weight change -4.2 kg +/-6.4 cf. -8.9 kg +/- 5.9, P = 0.03), greater radiotherapy completion rates (92% cf. 50%, P = 0.001), fewer patients had an unplanned hospital admission (46% cf. 75%, P = 0.04), and those that did had a shorter length of stay (3.2 days +/- 5.4 cf. 13.5 days +/- 14.1, P = 0.002). CONCLUSION: Early and regular nutrition assessment/intervention and a multidisciplinary approach to nutrition care results in improved treatment tolerance for patients with oesophageal cancer receiving chemoradiation.
Adult↗
Control of an outbreak of multi-drug-resistant Acinetobacter baumannii in an intensive care unit and a surgical ward.
We describe an outbreak of multi-drug-resistant Acinetobacter baumannii (MRAB) that occurred in an intensive care unit (ICU) and a surgical ward from December 2003 to March 2004. Mapping patient movements on a timeline indicated that the outbreak was confined to these two areas. Investigation by the hospital's infection prevention service found that a possible source of spread was improper cleaning methods used on respiratory equipment. Pulsed-field gel electrophoresis analysis of available isolates indicated the presence of two distinct strains. One strain was seen in patients from the ICU and the other strain was seen in the surgical ward patients. Cleaning and environmental decontamination as well as staff education were implemented to halt further immediate spread. The deficiencies identified during the investigation were also resolved. The final outcome was the successful termination of this outbreak.
Acinetobacter Infections↗
Historical correlates of genital herpes simplex virus type 2 infection in men attending an STD clinic.
BACKGROUND/OBJECTIVES: While nearly one in four Americans has antibodies to HSV-2, only one of 40 reports a history of genital herpes (GH). The goal of this study was to correlate questions designed to elicit a GH history with serological evidence of HSV-2 in male STD clinic attendees. METHODS: Consecutive males were enrolled in a study of the epidemiology of GH. Consenting men answered questionnaires regarding their histories of possible GH and underwent serological testing for HSV-1 and HSV-2. Association statistics between response to each question and HSV-2 serological status were calculated. RESULTS: Of 328 men enrolled, 148 (46%) had HSV-2 antibodies. 14 (4.3%) reported a history of GH when queried as part of a list of other STD (sensitivity (S) 0.08). 17 (5.2%) reported a history of GH when asked directly "Do you have genital herpes?" (S 0.09). 75 (21.1%) participants reported a history of a recurring genital sore, ulcer, or zipper cut (S 0.32). Overall, 64.2% of HSV-2 seropositive men answered "no" to all three questions. A "yes" response to any of the questions was only 36% sensitive for predicting HSV-2 infection. CONCLUSION: Few HSV-2 infected men report either a history of GH or are aware that they are infected. Asking about a history of recurrent genital sores was a more sensitive historical marker of HSV-2 infection than asking about a history of "genital herpes."
Adult↗
Transfusion-related acute lung injury (TRALI).
A 50-year-old male presented for a Whipple's procedure to excise a pancreatic lesion. Massive transfusion of packed cells and fresh frozen plasma was required. Towards the end of the procedure, the patient developed sudden onset of frank pulmonary oedema and hypotension. A presumptive diagnosis of transfusion related lung injury was made after prompt investigations excluded circulatory overload or cardiogenic shock as the cause. This case report describes an increasingly common and life-threatening sequela of blood product transfusion, the management of which is complicated by the current lack of specific diagnostic tests.
Humans↗
Metabonomics, dietary influences and cultural differences: a 1H NMR-based study of urine samples obtained from healthy British and Swedish subjects.
The aim of this study was to assess the feasibility and comparability of metabonomic data in clinical studies conducted in different countries without dietary restriction. A (1)H NMR-based metabonomic analysis was performed on urine samples obtained from two separate studies, both including male and female subjects. The first was on a group of healthy British subjects (n = 120), whilst the second was on healthy subjects from two European countries (Britain and Sweden, n = 30). The subjects were asked to provide single, early morning urine samples collected on a single occasion. The (1)H NMR spectra obtained for urine samples were visually inspected and analysed chemometrically using principal components analysis (PCA). These inspections highlighted outliers within the urine samples and displayed interesting differences, revealing characteristic dietary and cultural features between the subjects of both countries, such as high trimethylamine-N-oxide (TMAO)-excretion in the Swedish population and high taurine-excretion, due to the Atkins diet. This study suggests that the endogenous urinary profile is subject to distinct cultural and severe dietary influences and that great care needs to be taken in the interpretation of 'biomarkers of disease and response to drug therapy' for diagnostic purposes.
Adolescent↗
High-throughput genotyping of human platelet antigens using the 5'-nuclease assay and minor groove binder probe technology.
BACKGROUND AND OBJECTIVES: Human platelet antigen (HPA) genotyping is a valuable tool for typing platelets to assist in the management of alloimmunized thrombocytopenic patients. We describe, for the first time, 5' nuclease assays (NA) to genotype HPA-5 and -15, and improved 5'-NA to genotype HPA-1, -2 and -3, by utilizing minor groove binder (MGB) and non-fluorescent quencher (NFQ) technology. Superior probe specificity and fluorescent performance is attained through MGB-NFQ probe modifications compared with previous 5'-NA designs. MATERIALS AND METHODS: Primers and dye-labelled MGB-NFQ probes were designed and synthesized to detect the single nucleotide polymorphism responsible for each HPA-1, -2, -3, -5 and -15. One-hundred blood samples were tested for the combinations of HPA genotypes 1, 2, 3 and 5 by our traditional sequence-specific primer-polymerase chain reaction (SSP-PCR) method, and 41 blood samples were tested for HPA-15 by SSP-PCR at an external laboratory. These results were then compared with those obtained by using the new 5'-NA. RESULTS: There was complete concordance of results for all samples tested by SSP-PCR and 5'-NA. The 5'-NA offers distinct advantages over non-fluorescent genotyping methods. DNA amplification and allele discrimination occurs in a single closed tube for each antigen with no post-PCR manipulation required. This minimizes the risk of cross-contamination and mislabelling of samples, as well as making the assay less time-consuming to perform. In comparison with other fluorescent assays, the 5'-NA has the highest sample throughput, resulting from the use of a 96-well platform, identical cycling conditions for all assays and the potential for automation. CONCLUSIONS: Genotyping for HPA-1, -2, -3, -5, and -15 by the 5'-NA is suitable for routine analysis. The latest 5'-NA design, using MGB probe technology, ensures superior detection of all alleles and is the most versatile fluorescent assay, ideal for both urgent clinical samples and large-scale screening programs.
Antigens, Human Platelet↗
Coupling of oral human or porcine insulin to the B subunit of cholera toxin (CTB) overcomes critical antigenic differences for prevention of type I diabetes.
Our earlier investigations have demonstrated a critical difference in the efficacy of orally administered porcine compared to human or mouse insulin (no effect) in preventing type I diabetes in two distinct experimental models. Based on these findings one has to assume that certain insulins might not be suitable for the induction of oral 'tolerance'/bystander suppression, which might be one cause for recent failures in human oral antigen trials. Here we demonstrate that coupling to the non-toxic subunit of cholera toxin (CTB) can abolish these differences in efficacy between human and porcine insulin. As expected, an added benefit was the much smaller oral antigen dose required to induce CD4+ insulin-B specific regulatory cells that bystander-suppress autoaggressive responses. Mechanistically we found that uptake or transport of insulin-CTB conjugates in the gut occurs at least partially via binding to GM-1, which would explain the enhanced clinical efficacy. Both B chains bound well to major histocompatibility complex (MHC) class II, indicating comparable immunological potential once uptake and processing has occurred. Thus, our findings delineate a pathway to overcome issues in oral antigen choice for prevention of type I diabetes.
Administration, Oral↗
The cholera toxin B subunit is a mucosal adjuvant for oral tolerance induction in type 1 diabetes.
When conjugated to various proteins, the nontoxic B-chain of cholera toxin (CTB) significantly increases the ability of these proteins to induce immunological tolerance after oral administration. Here, we investigated if a nonconjugated form of CTB enhances the induction of immune tolerance after oral insulin administration. Induction of immunological tolerance was studied after oral administration of insulin preparations in three mouse models; an insulin/ovalbumin coimmunization model, a model of virus-induced diabetes in transgenic RIP-LCMV-NP mice and in nonobese diabetic (NOD) mice serving as a model of spontaneous diabetes. In the immunization model, we demonstrate that mixing with CTB increases the tolerogenic potential of insulin, approximately 10 fold. Titration of the CTB concentration in this system revealed that an insulin : CTB ratio of 100 : 1 was optimal for the induction of bystander suppression. Further studies revealed that this insulin : CTB ratio also was optimal for the prevention of diabetes in a virus-induced, transgenic diabetes model. In addition, the administration of this optimal insulin-CTB preparation significantly prevented the onset of diabetes in old NOD mice with established islet infiltration. The data presented here demonstrate that CTB, even in its unconjugated form, functions as a mucosal adjuvant, increasing the specific tolerogenic effect of oral insulin.
Adjuvants, Immunologic↗
NHS occupational health services in England and Wales--a changing picture.
AIMS: To establish the extent of doctor input to occupational health (OH) service provision in the UK National Health Service (NHS) in 2001 and to compare this with inputs in 1998. METHOD: A postal questionnaire was used to obtain information from OH medical staff employed by the NHS in England and Wales. RESULTS: The NHS OH service has seen an increase between 1998 and 2001 in the amount of doctor time per employee. Doctors tend to work now for more sessions per week. The proportion of doctors holding specialist qualifications has also increased. An increased number of NHS employees now have access to consultant care for occupational medicine. OH departments increasingly tend to provide services to employees beyond the NHS and are thereby able to generate income to further the development of the service. CONCLUSIONS: Steady progress is being made in improving the provision of OH services within the NHS. However, substantial variation exists in the apparent level of access to such provision. The government policy for all NHS staff to have access to a consultant-led service is not yet met. NHS Plus will impact on this picture and deserves study in the future.
England↗
Opioid dose requirements.
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Analgesics, Opioid↗
Do published criteria improve clinical diagnostic accuracy in multiple system atrophy?
OBJECTIVE: To assess the accuracy of a clinical diagnosis of multiple system atrophy (MSA) and compare it to the Quinn and Consensus criteria for MSA using neuropathologically examined cases from the Queen Square Brain Bank for Neurological Disorders. METHODS: Fifty-nine cases with a neurologic diagnosis of MSA when last assessed prior to death were studied. RESULTS: In 51 (86%) of these cases, the diagnosis of MSA was confirmed pathologically. False positive diagnoses included PD (n = 6), progressive supranuclear palsy (n = 1), and cerebrovascular disease (n = 1). When applying either set of diagnostic criteria, a diagnosis of probable MSA gave lower sensitivity but higher positive predictive value than one of possible MSA. Application of either set of diagnostic criteria was superior to actual clinical diagnosis made early in the disease, but there was little difference by the last clinic visit. CONCLUSIONS: This study shows a high diagnostic accuracy for the clinical diagnosis of MSA by neurologists, with PD accounting for most of the false positive diagnoses. Application of either Quinn or Consensus criteria was superior to actual clinical diagnosis made early in the disease, but there was little difference by last clinic visit.
Adult↗
Opponent and nonopponent contributions to the zebrafish electroretinogram using heterochromatic flicker photometry.
While some lower vertebrates, such as zebrafish, do not appear to possess anatomically separate pathways of processing visual information (such as M-pathways and P-pathways), it is believed that separate processing of the visual stimulus (such as luminance and chromatic processing) is a basic requirement of vertebrate vision. In this study, spectral sensitivity functions were obtained from electroretinogram responses to heterochromatic flicker photometry stimuli at several flicker rates, including a low flicker rate (2 Hz), in an attempt to predominantly stimulate chromatic processes and a high flicker rate (16 Hz), in an attempt to predominantly stimulate luminance processes. In addition, chromatic adaptation was used to isolate and examine the temporal properties of the different cone-type contributions to the electroretinogram response. Spectral sensitivity functions based on responses to heterochromatic stimuli of a low flicker rate appeared to receive both opponent and nonopponent contributions; however, when the stimulus flicker rate was high, spectral sensitivity appeared to be a function of only nonopponent mechanisms. Also, the differences in cone contributions to the spectral sensitivity functions across the different flicker rates appear to be related to the temporal properties of the cone contributions to the electroretinogram response.
Animals↗
Peripheral vascular disease is associated with abnormal arteriolar diameter relationships at bifurcations in the human retina.
Arterial diameters at branch points are believed to conform to design principles that optimize circulatory efficiency and maintain constant shear stress across arterial networks. The objective of this study was to examine whether optimality at bifurcations is affected in individuals with atherosclerosis. Retinal images were analysed in normotensive men with abnormal ankle brachial index (n=13) and healthy controls (n=8), matched for age and clinic blood pressure. Compared with controls, men with peripheral vascular disease had adverse metabolic profiles (relative insulin resistance and greater total cholesterol levels). In healthy men, retinal arterial diameters at bifurcations conformed to predicted optimal values but in men with peripheral vascular disease, junction exponents deviated significantly from the optimum. Retinal arteriolar bifurcation angles did not differ significantly between the groups. Atherosclerosis is associated with abnormalities in the arteriolar network of the retina. In view of the importance of the endothelium in maintaining network co-ordination of branch diameters this is suggestive of a generalized abnormality of endothelial function in atherosclerosis.
Adult↗
Anti-D immunoglobulin treatment for thrombocytopenia associated with primary antibody deficiency.
AIMS: To review our experience of anti-D immunoglobulin for immune thrombocytopenia (ITP) in patients with primary antibody deficiency. METHODS/PATIENTS: A retrospective case notes review of four Rhesus positive patients with ITP and primary antibody deficiency, treated with anti-D. Patients were refractory to steroids and high dose intravenous immunoglobulin (IVIG). Two patients were previously splenectomised. RESULTS: All patients responded to anti-D immunoglobulin. Improved platelet counts were sustained for at least three months. Side effects included a fall in haemoglobin in all cases; one patient required red blood cell transfusion. Two patients had transient neutropenia (< 1 x 10(9)/litre). CONCLUSION: Anti-D immunoglobulin may be an effective treatment for antibody deficiency associated thrombocytopenia, even after splenectomy. Anti-D immunoglobulin may have considerable clinical advantages in this group of patients, where treatments resulting in further immunosuppression are relatively contraindicated.
Adult↗
Plasmid vaccination with insulin B chain prevents autoimmune diabetes in nonobese diabetic mice.
The insulin B (InsB) chain bears major type 1 diabetes-associated epitopes of significance for disease in humans and nonobese diabetic (NOD) mice. Somatic expression of InsB chain initiated early in life by plasmid inoculation resulted in substantial protection of female NOD mice against disease. This was associated with a T2 shift in spleen, expansion of IL-4-producing and, to a lesser extent, of IFN-gamma-secreting T cells in pancreatic lymph nodes, as well as intermolecular Th2 epitope spreading to glutamic acid decarboxylase determinants. A critical role of IL-4 for the Ag-specific protective effect triggered by plasmid administration was revealed in female IL-4(-/-) NOD mice that developed diabetes and higher Th1 responses. Coadministration of IL-4-expressing plasmid or extension of the vaccination schedule corrected the unfavorable response of male NOD mice to DNA vaccination with InsB chain. Thus, plasmid-mediated expression of the InsB chain early in diabetes-prone mice has the potential to prevent transition to full-blown disease depending on the presence of IL-4.
Animals↗
Low-copy-number human transgene is recognized as an X inactivation center in mouse ES cells, but fails to induce cis-inactivation in chimeric mice.
X chromosome inactivation is initiated from a segment of the mammalian X chromosome called the X inactivation center. Transgenes from this region of the murine X chromosome are providing the means to identify the DNA needed for cis inactivation in mice. We recently showed that chimeric mice carrying transgenes from the human X inactivation center (XIC) region also provide a functional assay for human XIC activity; approximately 6 copies of a 480-kb human transgene (ES-10) were sufficient to initiate random X inactivation in cells of male chimeric mice (Migeon et al., 1999, Genomics, 59, 113-121). Now, we report studies of another human transgene (ES-5), which contains less than 300 kb of the human XIC region on Xq13.2 including an intact XIST locus and which has inserted in one or two copies into mouse chromosome 6. The ES-5 transgene is recognized as an X inactivation center in mouse embryonic stem cells, but is not sufficient to induce random X inactivation in somatic cells of highly chimeric mice. Human transgenes in chimeric mice provide a means to uncouple the key steps in this complex pathway and facilitate the search for essential components of the human XIC region.
Animals↗