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1.
J Surg Case Rep ; 2022(6): rjac260, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35733976

ABSTRACT

A 38-year-old male with sickle cell trait and acute refractory heart failure received an axillary intra-aortic balloon pump and short-term biventricular assist device. He underwent orthotopic heart transplantation 45 days later, which was complicated by major bleeding necessitating significant intra-operative transfusion. Support with veno-arterial extracorporeal membrane oxygenation was provided and successfully weaned five days later. He made a full recovery and remains alive and well 34 months after discharge. We hypothesize that the protective peri-operative measures undertaken, including normothermia during surgery and post-operative haemodynamic stability due to the use of mechanical circulatory support, conveyed a degree of protection against complications associated with sickle cell dysfunction and contributed to the successful outcome.

2.
J Biol Chem ; 296: 100352, 2021.
Article in English | MEDLINE | ID: mdl-33524389

ABSTRACT

Many bacteria produce polysaccharide-based capsules that protect them from environmental insults and play a role in virulence, host invasion, and other functions. Understanding how the polysaccharide components are synthesized could provide new means to combat bacterial infections. We have previously characterized two pairs of homologous enzymes involved in the biosynthesis of capsular sugar precursors GDP-6-deoxy-D-altro-heptose and GDP-6-OMe-L-gluco-heptose in Campylobacter jejuni. However, the substrate specificity and mechanism of action of these enzymes-C3 and/or C5 epimerases DdahB and MlghB and C4 reductases DdahC and MlghC-are unknown. Here, we demonstrate that these enzymes are highly specific for heptose substrates, using mannose substrates inefficiently with the exception of MlghB. We show that DdahB and MlghB feature a jellyroll fold typical of cupins, which possess a range of activities including epimerizations, GDP occupying a similar position as in cupins. DdahC and MlghC contain a Rossman fold, a catalytic triad, and a small C-terminal domain typical of short-chain dehydratase reductase enzymes. Integrating structural information with site-directed mutagenesis allowed us to identify features unique to each enzyme and provide mechanistic insight. In the epimerases, mutagenesis of H67, D173, N121, Y134, and Y132 suggested the presence of alternative catalytic residues. We showed that the reductases could reduce GDP-4-keto-6-deoxy-mannulose without prior epimerization although DdahC preferred the pre-epimerized substrate and identified T110 and H180 as important for substrate specificity and catalytic efficacy. This information can be exploited to identify inhibitors for therapeutic applications or to tailor these enzymes to synthesize novel sugars useful as glycobiology tools.


Subject(s)
Bacterial Proteins/metabolism , Campylobacter jejuni/metabolism , Heptoses/metabolism , Oxidoreductases/metabolism , Racemases and Epimerases/metabolism , Bacterial Proteins/chemistry , Campylobacter Infections/microbiology , Campylobacter jejuni/chemistry , Heptoses/chemistry , Humans , Oxidoreductases/chemistry , Protein Conformation , Racemases and Epimerases/chemistry , Substrate Specificity
3.
Interact Cardiovasc Thorac Surg ; 32(4): 625-631, 2021 04 19.
Article in English | MEDLINE | ID: mdl-33313866

ABSTRACT

OBJECTIVES: Primary graft dysfunction after heart transplant is associated with high morbidity and mortality. Extracorporeal membrane oxygenation (ECMO) can be used to wean patients from cardiopulmonary bypass. This study retrospectively reviews a single-centre experience of post-transplant ECMO in regard to outcomes and associated costs. METHODS: Between May 2006 and May 2019, a total of 267 adult heart transplants were performed. We compared donor and recipient variables, ECMO duration and the incidence of renal failure, bleeding, infection and cost analysis between ECMO and non-ECMO groups. RESULTS: ECMO support was required postoperatively to manage primary graft dysfunction in 72 (27%) patients. The mean duration of ECMO support was 6 ± 3.2 days. Mean ischaemic times were similar between the groups. There was a significantly higher proportion of ventricular assist device explant to transplant in the ECMO group versus non-ECMO (38.2% vs 14.1%; P < 0.0001). ECMO patients had a longer duration of stay in the intensive care unit (P < 0.0001) and total hospital stay (P < 0.0001). Greater mortality was observed in the ECMO group (P < 0.0001). The median cost of providing ECMO was £18 000 [interquartile range (IQR): £12 750-£24 000] per patient with an additional median £35 225 (IQR: £21 487.25-£51 780.75) for ITU stay whilst on ECMO. The total median cost per patient inclusive of hospital stay, ECMO and dialysis costs was £65 737.50 (IQR: £52 566.50-£95 221.75) in the non-ECMO group compared to £145 415.71 (IQR: £102 523.21-£200 618.96) per patient in the ECMO group (P < 0.0001). CONCLUSIONS: Patients with primary graft dysfunction following heart transplantation who require ECMO are frequently bridged to a recovery; however, the medium and longer-term survival for these patients is poorer than for patients who do not require ECMO.


Subject(s)
Extracorporeal Membrane Oxygenation , Heart Transplantation , Extracorporeal Membrane Oxygenation/adverse effects , Heart Transplantation/adverse effects , Heart-Assist Devices , Humans , Primary Graft Dysfunction , Retrospective Studies , Treatment Outcome
4.
J Heart Lung Transplant ; 39(4): 342-352, 2020 04.
Article in English | MEDLINE | ID: mdl-32029401

ABSTRACT

BACKGROUND: Patients with cardiogenic shock (CS) needing temporary circulatory support (TCS) have poor survival rates after implantation of durable ventricular assist device (dVAD). We aimed to characterize post-dVAD adverse event burden and survival rates in patients requiring pre-operative TCS. METHOD: We analyzed 13,511 adults (Interagency Registry for Mechanically Assisted Circulatory Support [INTERMACS] Profiles 1-3) with continuous-flow dVADs in International Society for Heart and Lung Transplantation Registry for Mechanically Assisted Circulatory Support (2013-2017) according to the need for pre-operative TCS (n = 5,632) vs no TCS (n = 7,879). Of these, 726 (5.4%) had biventricular assist devices (BiVAD). Furthermore, we compared prevalent rates (events/100 patient-months) of bleeding, device-related infection, hemorrhagic and ischemic cerebrovascular accidents (hemorrhagic cerebral vascular accident [hCVA], and ischemic cerebral vascular accident [iCVA]) in early (<3 months) and late (≥3 months) post-operative periods. RESULTS: TCS included extracorporeal membrane oxygenation (ECMO) (n = 1,138), intra-aortic balloon pump (IABP) (n = 3,901), and other TCS (n = 593). Within 3 post-operative months, there were more major bleeding and cerebrovascular accidents (CVAs) in patients with pre-operative ECMO (events/100 patient-months rates: bleeding = 19, hCVA = 1.6, iCVA = 2.8) or IABP (bleeding = 17.3, hCVA = 1.5, iCVA = 1.5) vs no TCS (bleeding = 13.2, hCVA = 1.1, iCVA = 1.2, all p < 0.05). After 3 months, adverse events were lower and similar in all groups. Patients with ECMO had the worst short- and long-term survival rates. Patients with BiVAD had the worst survival rate regardless of need for pre-operative TCS. CVA and multiorgan failures were the common causes of death for patients with TCS and patients without TCS. CONCLUSIONS: Patients requiring TCS before dVAD had a sicker phenotype and higher rates of early post-operative adverse events than patients without TCS. ECMO was associated with very high early ischemic stroke, bleeding, and mortality. The extreme CS phenotype needing ECMO warrants a higher-level profile status, such as INTERMACS "0."


Subject(s)
Extracorporeal Membrane Oxygenation/adverse effects , Heart Failure/therapy , Heart Transplantation , Heart-Assist Devices/adverse effects , Intra-Aortic Balloon Pumping/adverse effects , Registries , Aged , Female , Global Health , Heart Failure/mortality , Humans , Male , Middle Aged , Survival Rate/trends
5.
J Heart Lung Transplant ; 39(2): 145-156, 2020 02.
Article in English | MEDLINE | ID: mdl-31866174

ABSTRACT

BACKGROUND: Patients with advanced heart failure and cardiogenic shock (CS) often require temporary circulatory support (TCS) as a bridge to durable ventricular assist devices (dVADs). We aim to characterize longitudinal outcomes of patients with and without CS. METHODS: Between 2013 and 2017, 13,813 adult patients classified as Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Profiles 1 to 3 with continuous flow left ventricular assist devices or biventricular assist devices were registered into the International Society for Heart and Lung Transplantation Registry for Mechanically Assisted Circulatory Support. Patients were sub-grouped according to support type (extracorporeal membrane oxygenation [ECMO], intra-aortic balloon pump [IABP], and other TCS). Other TCS included all other surgical and percutaneous TCS devices. Estimated survival was compared based on need for pre-operative TCS and by profile. RESULTS: Pre-operative TCS was used in 5,632 (41%) cases. Of these, ECMO was used in 1,138 (20%) cases, IABP in 3,901 (69%) cases, and other TCS in 595 (11%) cases. Patients requiring ECMO had greater needs for biventricular support after dVAD (22% ECMO, 5% IABP, and 7% other TCS; p < 0.001) with longer post-implant intensive care stays (ECMO 24 days, IABP 14 days, and other TCS 12 days; p < 0.001). INTERMACS Profile 1 to 3 patients with pre-implant ECMO had the lowest longitudinal survival (82% at 1 month and 44% at 48 months) compared with IABP (93% at 1 month and 51% at 48 months), other TCS (92% at 1 month and 52% at 48 months), and non-TCS (95% at 1 months and 55 % at 48 months) (p < 0.0001). Propensity score matching analysis of the pre-implant ECMO INTERMACS Profile 1 group when compared with alternative pre-implant TCS strategies had an associated higher hazard impacting early phase survival vs other TCS (hazard ratio, 1.80; p < 0.01) and IABP (hazard ratio, 1.65; p < 0.01). CONCLUSIONS: In advanced heart failure with patients with CS, the use of ECMO before dVAD was associated with lower longitudinal survival and increased utilization of biventricular support compared with alternative TCS strategies. Research focused on longitudinal profiling in CS and pre-implant TCS is warranted to further understand these differences.


Subject(s)
Extracorporeal Membrane Oxygenation/instrumentation , Heart Failure/complications , Heart-Assist Devices , Propensity Score , Registries , Shock, Cardiogenic/therapy , Equipment Design , Female , Follow-Up Studies , Heart Failure/diagnosis , Heart Failure/therapy , Humans , Male , Middle Aged , Retrospective Studies , Shock, Cardiogenic/diagnosis , Shock, Cardiogenic/etiology , Treatment Outcome
6.
Arch Phys Med Rehabil ; 99(10): 2022-2029, 2018 10.
Article in English | MEDLINE | ID: mdl-29698641

ABSTRACT

OBJECTIVE: This study evaluated the relationship between physiological and perceived fall risk in people with multiple sclerosis (MS). DESIGN: Secondary analysis of data from prospective cohort studies undertaken in Australia, the United Kingdom, and the United States. SETTING: Community. PARTICIPANTS: Ambulatory people with MS (N=416) (age 51.5±12.0 years; 73% female; 62% relapsing-remitting MS; 13.7±9.9 years disease duration). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: All participants completed measures of physiological (Physiological Profile Assessment [PPA]) and perceived (Falls Efficacy Scale-international [FESi]) fall risk and prospectively recorded falls for 3 months. RESULTS: 155 (37%) of the participants were recurrent fallers (≥2 falls). Mean PPA and FESi scores were high (PPA 2.14±1.87, FESi 34.27±11.18). The PPA and the FESi independently predicted faller classification in logistic regression, which indicated that the odds of being classified as a recurrent faller significantly increased with increasing scores (PPA odds ratio [OR] 1.30 [95% CI 1.17-1.46], FESi OR 1.05 [95% CI 1.03-1.07]). Classification and regression tree analysis divided the sample into four groups based on cutoff values for the PPA: (1) low physiological/low perceived risk (PPA <2.83, FESi <27.5), (2) low physiological/high perceived risk (PPA <2.83, FESi >27.5), (3) high physiological/low perceived risk (PPA >2.83, FESi <35.5), and (4) high physiological/high perceived risk (PPA <2.83, FESi >35.5). Over 50% of participants had a disparity between perceived and physiological fall risk; most were in group 2. It is possible that physiological risk factors not detected by the PPA may also be influential. CONCLUSIONS: This study highlights the importance of considering both physiological and perceived fall risk in MS and the need for further research to explore the complex interrelationships of perceptual and physiological risk factors in this population. This study also supports the importance of developing behavioral and physical interventions that can be tailored to the individual's needs.


Subject(s)
Accidental Falls/statistics & numerical data , Multiple Sclerosis/physiopathology , Multiple Sclerosis/psychology , Adult , Aged , Australia/epidemiology , Female , Humans , Logistic Models , Male , Middle Aged , Odds Ratio , Perception , Prospective Studies , Risk Assessment , Risk Factors , United Kingdom/epidemiology , United States/epidemiology
7.
Vet Dermatol ; 29(3): 192-e70, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29664197

ABSTRACT

BACKGROUND: Antimicrobial-resistant bacteria are increasingly isolated from veterinary patients. OBJECTIVES: To determine risk factors for antimicrobial resistance (AMR) among canine mucosal staphylococci following routine antimicrobial treatment with cefalexin (CFX), clavulanate-amoxicillin (AC), cefovecin (CVN), clindamycin (CD) or a fluoroquinolone (FQ). ANIMALS: Mucosal swab samples (n = 463) were collected from 127 dogs pre-treatment, immediately, and at one- and three-months post-treatment. METHODS: Staphylococci were identified phenotypically and biochemically as coagulase negative (CoNS) or coagulase positive (CoPS); CoPS were speciated by nuc gene PCR. Antimicrobial susceptibility was determined using disc diffusion and mecA gene carriage by PCR. Multilevel, multivariable models examined associations between risk factors and presence/absence of CoPS, meticillin resistance (MR), multidrug-resistance (MDR) and fluoroquinolone resistance (FQR). RESULTS: The percentage of samples with CoNS increased and with CoPS (including S. pseudintermedius) decreased immediately post-treatment with CFX, CVN and CD (P ≤ 0.001) and one month post-treatment with CD (P = 0.003). By three months post-treatment, there was no significant difference compared to pre-treatment samples. Immediately post-treatment with FQs there was significantly increased risk of isolating MRS (P = 0.002), MDR (P = 0.002) or FQR (P = 0.013) staphylococci and of MDR following CFX treatment (P = 0.019). The percentage of samples with AMR staphylococci declined from immediately to three months post-treatment and there was no significant difference between resistance prevalence at one or three months post-treatment for most AMR traits and treatment groups. Exceptions include increased MDR following FQ (P = 0.048) or CFX (P = 0.021), at one and three months post-treatment, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Systemic antimicrobials impact on mucosal staphylococci. Immediately after therapy, the mucosa may be a reservoir for AMR staphylococci that are a source of mobile genetic elements carrying AMR genes.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Dog Diseases/drug therapy , Staphylococcal Infections/veterinary , Animals , Dog Diseases/microbiology , Dogs , Drug Resistance, Multiple, Bacterial/genetics , England , Methicillin Resistance , Microbial Sensitivity Tests , Mucous Membrane/microbiology , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Staphylococcus/drug effects , Staphylococcus/genetics
8.
J Interpers Violence ; 31(12): 2175-95, 2016 07.
Article in English | MEDLINE | ID: mdl-25724877

ABSTRACT

The attrition of rape cases from the criminal justice system (CJS) remains high and there is a paucity of research in relation to marginalized groups. Sex workers (SWs) are vulnerable to sexual violence due to the nature of their work. They are also unlikely to report such violence to police for a range of reasons. Two stages of research sought to describe the victim, perpetrator, and offense characteristics of SW rape and to examine the attrition of these cases. All rapes and attempted rapes (N = 1,146) reported to police in a large city in the South West of England over a 21-year period were examined; 67 cases involved SWs. Data were extracted from police files in line with the variables of interest. Secondary analysis of the total number of SW rapes (n = 67) resulted in a profile of these cases. A matched pairs study revealed significant differences in victim, perpetrator, and assault characteristics between SW (n = 62) and non-sex-worker (NSW) samples (n = 62). Although no significant difference was found in terms of attrition from the CJS, SW cases were observed to secure more convictions for rape than NSW cases. The implications of the findings for practice and future research are discussed.


Subject(s)
Crime Victims/legislation & jurisprudence , Rape/legislation & jurisprudence , Sex Workers/legislation & jurisprudence , Adolescent , Adult , Female , Humans , Middle Aged , Young Adult
9.
J Foot Ankle Res ; 8: 66, 2015.
Article in English | MEDLINE | ID: mdl-26617676

ABSTRACT

BACKGROUND: Health profession students develop practical skills whilst integrating theory with practice in a real world environment as an important component of their training. Research in the area of practice placements has identified challenges and barriers to the delivery of effective placement learning. However, there has been little research in podiatry and the question of which factors impact upon clinical educators' capacity to engage with the role remains an under-researched area. This paper presents the second phase of an action research project designed to determine the factors that impact upon clinical educators' capacity to engage with the mentorship role. METHODS: An online survey was developed and podiatry clinical educators recruited through National Health Service (NHS) Trusts. The survey included socio-demographic items, and questions relating to the factors identified as possible variables influencing clinical educator capacity; the latter was assessed using the 'Clinical Educator Capacity to Engage' scale (CECE). Descriptive statistics were used to explore demographic data whilst the relationship between the CECE and socio-demographic factors were examined using inferential statistics in relation to academic profile, career profile and organisation of the placement. RESULTS: The survey response rate was 42 % (n = 66). Multiple linear regression identified four independent variables which explain a significant proportion of the variability of the dependent variable, 'capacity to engage with clinical education', with an adjusted R2 of 0.428. The four variables were: protected mentorship time, clinical educator relationship with university, sign-off responsibility, and volunteer status. CONCLUSION: The identification of factors that impact upon clinical educators' capacity to engage in mentoring of students has relevance for strategic planning and policy-making with the emphasis upon capacity-building at an individual level, so that the key attitudes and characteristics that are linked with good clinical supervision are preserved.

10.
J Med Virol ; 87(7): 1207-17, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25908236

ABSTRACT

HCV is a major cause of liver disease worldwide. IL-12 plays an essential role in the balance of T helper 1 (Th1) differentiation versus a T helper 2 (Th2) driven response from its naïve precursor. Linkage disequilibrium measures the degree to which alleles at two loci are associated and the non-random associations between alleles at two loci. Haplotypes of the three IL-12B loci studied were determined in the patient cases and the normal healthy control subjects. The frequency of the 12 possible IL-12B haplotypes on the 3 loci was determined in subjects heterozygous at only one of the loci within the studied haplotype. Haplotype frequencies were compared between the patient groups and controls (n = 49) to determine if any preferential combination of markers occurred using chi-squared and applying the Bonferroni correction. 45 HCV RNA negative patients; 88 HCV RNA positive patients; and 15 uninfected cases at high risk of HCV infection (EU) were studied. The haplotype "C" SNP of the 3'UTR with the "E" 4 bp deletion of the intron 4 region was in linkage disequilibrium (χ(2) = 45.15, P < 0.001, 95% CL). The haplotype analysis of the insertion allele of the promoter with the deletion allele of the intron 4("E") IL-12B polymorphism showed linkage disequilibrium (χ(2) = 5.64, P = 0.02). Linkage disequilibrium of polymorphisms is reported in the IL-12 gene in patients with HCV infection and contributes to the understanding of patient genotype and expected production of IL-12, responding to infection.


Subject(s)
Haplotypes , Hepatitis C/genetics , Interleukin-12/genetics , Linkage Disequilibrium , Polymorphism, Genetic , 3' Untranslated Regions , Base Sequence , Female , Gene Frequency , Hepacivirus/genetics , Hepacivirus/immunology , Hepatitis C/immunology , Hepatitis C/virology , Humans , Interleukin-12 Subunit p40/genetics , Introns , Male , Molecular Sequence Data , Promoter Regions, Genetic
11.
Gene ; 569(1): 41-5, 2015 Sep 10.
Article in English | MEDLINE | ID: mdl-25858271

ABSTRACT

UNLABELLED: The effective treatment of diabetes and the prevention of diabetic complications may be improved by a better understanding of the antioxidant function of intracellular defences against oxidative stress. Polymorphisms in antioxidant genes may determine cellular oxidative stress levels as a primary pathogenic role in diabetes and/or in its complications. SOD-2 was investigated in patients with type 1 diabetes mellitus (T1DM) to ascertain if specific genotypes have any protective influences in the pathogenic mechanisms in diabetes and/or in several different complications, including retinopathy, nephropathy and diabetic controls compared to normal healthy controls. METHOD: 278 (136M:142F) T1DM patients and 135 (72M:63F) normal, healthy controls were investigated for SOD-2 polymorphism in the mitochondrial targeting sequence with Ala/Val (C-9T) substitution. RESULTS: A significant difference in the C-9-T genotype was observed between patients and normal controls but not between diabetic controls and patients with complications. There were significantly more of the diabetic control (DC, n=62) group (11.3%) than the patients with diabetic nephropathy (DN, n=73) (1.4%) with the CC genotype (p=0.03 and χ(2)=4.27, OR=9.16 (1.08

Subject(s)
Diabetes Mellitus, Type 1/genetics , Diabetic Nephropathies/genetics , Oxidative Stress/genetics , Superoxide Dismutase/genetics , Adult , Antioxidants/metabolism , Diabetes Complications/genetics , Diabetes Complications/pathology , Diabetes Mellitus, Type 1/pathology , Diabetic Nephropathies/pathology , Female , Gene Frequency , Genetic Association Studies , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide , Superoxide Dismutase/metabolism
12.
J Med Virol ; 86(6): 941-7, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24610415

ABSTRACT

Hepatitis C virus (HCV) is a pathogen causing chronic hepatitis, cirrhosis, and liver cancer occurring in about 3% of the world's population. Most individuals infected with HCV develop persistent viremia. Oxidative stress may play an important role in the pathogenesis of a number of diseases including HCV infection and diabetes mellitus. Polymorphisms in the antioxidant genes may determine cellular oxidative stress levels as a primary pathogenic role in HCV and/or in its complications. Patients with HCV and normal, healthy controls were investigated for a superoxide dismutase (SOD-2) polymorphism in the mitochondrial targeting sequence with Ala/Val (C-9T) substitution. Polymorphisms in antioxidant gene SOD-2 were carried out by PCR, restriction fragment length polymorphism assays and by polyacrylamide gel electrophoresis. For the SOD-2 polymorphism, the RNA positive group showed a higher percentage of "CT" genotype than the RNA negative group (89.3% vs. 66.1%, P = 0.001, χ(2) = 11.9). The RNA negative group had more TT genotypes than the RNA positive group (27.4% vs. 6.80%, P = 0.01, χ(2) = 11.6). The exposed uninfected group had an increased frequency of the "CT" genotype (86.2% vs. 66.1%, P = 0.02, χ(2) = 5.5). The RNA positives had a higher frequency of the "CT" from the normal controls (72.1% vs. 89.2%, P = 0.005, χ(2) = 7.8).


Subject(s)
Genetic Predisposition to Disease , Hepacivirus/immunology , Hepatitis C/immunology , Superoxide Dismutase/genetics , Superoxide Dismutase/metabolism , Adult , Electrophoresis, Polyacrylamide Gel , Female , Humans , Male , Middle Aged , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Polymorphism, Single Nucleotide , Retrospective Studies
13.
Ther Apher Dial ; 18(1): 31-6, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24267593

ABSTRACT

Hypophosphatemia is well recognized in the intensive care setting, associated with refeeding and continuous forms of renal replacement therapy (CCRT). However, it is unclear as to when and how to administer intravenous phosphate supplementation in the general intensive care setting. There have been recent concerns regarding phosphate administration and development of acute kidney injury. We therefore audited our practice of parenteral phosphate administration. We prospectively audited parenteral phosphate administration (20 mmol) in 58 adult patients in a general intensive care unit in a University tertiary referral center. Fifty-eight patients were audited; mean age 57.2 ± 2.0 years, 70.7% male. The median duration of the infusion was 310 min (228-417), and 50% of the patients were on CRRT. 63.8% of patients were hypophosphatemic (<0.87 mmol/L) prior to the phosphate infusion, and serum phosphate increased from 0.79 ± 0.02 to 1.07 ± 0.03 mmol/L, P < 0.001. Two patients became hyperphosphatemic (>1.45 mmol/L). There was no correlation between the change in serum phosphate and the pre-infusion phosphate. Although there were no significant changes in serum urea, creatinine or other electrolytes, arterial ionized calcium fell from 1.15 ± 0.01 to 1.13 ± 0.01 mmol/L, P < 0.01. Although infusion of 20 mmol phosphate did not appear to adversely affect renal function and corrected hypophosphatemia in 67.7% of cases, we found that around 33% of patients who were given parenteral phosphate were not hypophosphatemic, and that the fall in ionized calcium raises the possibility of the formation of calcium-phosphate complexes and potential for soft tissue calcium deposition.


Subject(s)
Calcium/metabolism , Hypophosphatemia/drug therapy , Intensive Care Units , Phosphates/administration & dosage , Renal Replacement Therapy , Calcium Phosphates/chemistry , Female , Humans , Hyperphosphatemia/chemically induced , Hyperphosphatemia/epidemiology , Male , Middle Aged , Phosphates/adverse effects , Phosphates/therapeutic use , Prospective Studies , Time Factors , Treatment Outcome
14.
Transpl Immunol ; 28(2-3): 81-5, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23481351

ABSTRACT

Acute rejection remains associated with poor graft outcome. An early predictor of acute renal transplant rejection is the long sought after goal for transplant immunologists. In this study we measured levels of serum neopterin at day 5 post-transplant in a cohort of 216 consecutive renal allograft recipients, and compared this with serum creatinine and acute rejection episodes during the first year post transplant. We compared serum neopterin in recipients from living donors (LD), donors after brain death (DBD) and donors after cardiac death (DCD). In all cases higher neopterin levels were correlated with acute rejection in the first year post transplant, but this was only significant in recipients of DCD kidneys who suffered acute cellular or vascular rejection (p=0.04, odds ratio 1.08, 95% CI 1.003-1.012). The neopterin/creatinine ratio, which takes into account the effect of kidney function on circulating neopterin levels, was significantly higher for all recipients who suffered biopsy proven cellular or vascular rejection in the first year post transplant, compared to all other patients (p=0.001, for an increase of 0.1, odds ratio=1.64, 95% CI 1.21-2.20). The ability to use non-invasive biomarkers in the transplant recipient has the potential to increase transplant survival for these patients.


Subject(s)
Graft Rejection/immunology , Kidney Transplantation , Neopterin/blood , Adolescent , Adult , Aged , Creatine/blood , Female , Humans , Male , Middle Aged , Risk Factors , Time Factors , Young Adult
15.
Diving Hyperb Med ; 42(4): 201-7, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23258456

ABSTRACT

INTRODUCTION: Scuba diving demands information processing, recall, reasoning, decision making and the ability to take control of situations under different scenarios. Anecdotal evidence suggests that some divers consume alcohol to excess around the time of a dive. This study investigates alcohol consumption and attitudes to alcohol in United Kingdom (UK) recreational divers. METHODS: A questionnaire addressing diving demographics, general health, type and frequency of alcohol consumption, and attitudes to drinking alcohol around the time of diving was available for anonymous completion online between September 2010 and January 2011. RESULTS: Records from 818 divers were analysed. Older divers were more likely to exceed the weekly alcohol units recommended by the UK government compared to younger divers (P < 0.001), but binge drinking was associated with younger divers (P = 0.014). Diving when considering themselves unfit to drive a car was reported by 151 (18.5%) respondents and 187 (22.9%) had witnessed a diving incident which they felt was attributable to alcohol. Only 313 (38.3%) respondents reported a responsible attitude to alcohol by their dive clubs both under normal circumstances and whilst on a dive trip. CONCLUSION: Some divers undertook diving activities when potentially over the legal limit to drive a car and demonstrated a possible lack of understanding of the effects of alcohol beyond dehydration. Divers considered club attitudes to drinking and diving to be less responsible when on a diving trip. Some divers took a more responsible attitude to alcohol consumption having witnessed a diving incident which was potentially related to alcohol.


Subject(s)
Alcohol Drinking/epidemiology , Diving/statistics & numerical data , Health Knowledge, Attitudes, Practice , Adolescent , Adult , Age Distribution , Age Factors , Aged , Alcohol Drinking/adverse effects , Alcohol Drinking/legislation & jurisprudence , Automobile Driving/standards , Binge Drinking/epidemiology , Binge Drinking/legislation & jurisprudence , Binge Drinking/psychology , Diving/psychology , Female , Government Regulation , Humans , Male , Middle Aged , Qualitative Research , Recreation/psychology , Reference Standards , Sex Distribution , Surveys and Questionnaires , United Kingdom/epidemiology , Young Adult
16.
Liver Transpl ; 18(4): 405-12, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22213443

ABSTRACT

Acetaminophen-induced acute liver failure (ALF) is a complex multiorgan illness. An assessment of the prognosis is essential for the accurate identification of patients for whom survival without liver transplantation (LT) is unlikely. The aims of this study were the comparison of prognostic models [King's College Hospital (KCH), Model for End-Stage Liver Disease, Sequential Organ Failure Assessment (SOFA), and Acute Physiology and Chronic Health Evaluation II (APACHE II)] and the identification of independent prognostic indicators of outcome. We evaluated consecutive patients with severe acetaminophen-induced ALF who were admitted to the intensive care unit. At admission, demographic, clinical, and laboratory parameters were recorded. The discriminative ability of each prognostic score at the baseline was evaluated with the area under the receiver operating characteristic curve (AUC). In addition, using a multiple logistic regression, we assessed independent factors associated with outcome. In all, 125 consecutive patients with acetaminophen-induced ALF were evaluated: 67 patients (54%) survived with conservative medical management (group 1), and 58 patients (46%) either died without LT (28%) or underwent LT (18%; group 2). Group 1 patients had significantly lower median APACHE II (10 versus 14) and SOFA scores (9 versus 12) than group 2 patients (P < 0.001). The independent indicators associated with death or LT were a longer prothrombin time (P = 0.007), the inspiratory oxygen concentration (P = 0.005), and the lactate level at 12 hours (P < 0.001). The KCH criteria had the highest specificity (83%) but the lowest sensitivity (47%), and the SOFA score had the best discriminative ability (AUC = 0.79). In conclusion, for patients with acetaminophen-induced ALF, the SOFA score performed better than the other prognostic scores, and this reflected the presence of multiorgan dysfunction. A further evaluation of SOFA with the KCH criteria is warranted.


Subject(s)
Acetaminophen/adverse effects , Analgesics, Non-Narcotic/adverse effects , Chemical and Drug Induced Liver Injury/diagnosis , Health Status Indicators , Liver Failure, Acute/diagnosis , Multiple Organ Failure/diagnosis , APACHE , Adult , Biomarkers/blood , Chemical and Drug Induced Liver Injury/blood , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/mortality , Chemical and Drug Induced Liver Injury/surgery , Female , Humans , Lactic Acid/blood , Liver Failure, Acute/blood , Liver Failure, Acute/chemically induced , Liver Failure, Acute/mortality , Liver Failure, Acute/surgery , Liver Transplantation , Logistic Models , London , Male , Middle Aged , Multiple Organ Failure/blood , Multiple Organ Failure/chemically induced , Multiple Organ Failure/mortality , Multiple Organ Failure/surgery , Multivariate Analysis , Odds Ratio , Patient Selection , Predictive Value of Tests , Prognosis , Prospective Studies , ROC Curve , Risk Assessment , Risk Factors , Severity of Illness Index , Time Factors , Young Adult
17.
Diving Hyperb Med ; 41(1): 9-15, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21560979

ABSTRACT

AIMS: Anecdotal observations suggest the use of illicit drugs takes place amongst recreational divers but, to date, there has been little open debate within the diving community concerning possible prevalence. This study investigated the prevalence and type of illicit drugs used by recreational divers in the United Kingdom (UK). METHODS: Anonymous questionnaires were circulated via UK dive clubs, dive schools, dive shows and conferences. Questions incorporated diver and diving demographics and general health, which included anxiety, depression and panic attacks, alcohol use, smoking and illicit drug use since learning to dive and closest time to a dive. Questions pertaining to over-the-counter and prescription drug use were also asked. RESULTS: 479 divers responded (66% males and 34% females) in the age range 16 to 59 years. Of the respondents, 22% had used one or more illicit drug since learning to dive, reporting benzodiazepines, amphetamines, cocaine, ecstasy, LSD, cannabis, heroin, and 'magic mushrooms'. Illicit drugs had been used by 3.5% of respondents in the last 12 months, and 3% in the last month. Cannabis, cocaine and ecstasy use was reported within 6 hours of a dive. Logistic regression confirmed a relationship between illicit drug use and depression (P = 0.014), and also between illicit drug use and anxiety (P = 0.024). CONCLUSION: These data support anecdotal reports that recreational divers use a range of illicit drugs. The significant relationship between illicit drug use and depression and anxiety supports the literature in non-diving populations.


Subject(s)
Diving/statistics & numerical data , Substance-Related Disorders/epidemiology , Adolescent , Adult , Anxiety/epidemiology , Anxiety/psychology , Depression/epidemiology , Depression/psychology , Diving/psychology , Female , Humans , Logistic Models , Male , Middle Aged , United Kingdom/epidemiology , Young Adult
18.
J Interpers Violence ; 26(11): 2303-20, 2011 Jul.
Article in English | MEDLINE | ID: mdl-20956439

ABSTRACT

This study examines victim, offender, and offence characteristics associated with sexual assaults by strangers of older women compared to those against younger women. Cases are obtained from the Serious Crime Analysis Section of the United Kingdom National Policing Improvement Agency (NPIA; formerly Centrex). All possible cases of rape, attempted rape, and lesser sexual assault involving a single female victim aged 60 or older are selected (n = 53). These are matched with a sample of sexual assaults against women aged between 20 to 45 years ( n = 53). Research findings reveal significant differences in relation to a number of variables, including ethnicity of the offender, number of previous convictions of the offender, and characteristics associated with the assault itself. The results of this research reveal new information about violent sexual assaults on older women by strangers and have implications for practitioners dealing with such cases.


Subject(s)
Crime Victims/psychology , Crime Victims/statistics & numerical data , Criminals/psychology , Sex Offenses/psychology , Sex Offenses/statistics & numerical data , Adult , Age Distribution , Aged , Aged, 80 and over , Criminal Psychology , Databases, Factual , Female , Humans , Interpersonal Relations , Middle Aged , Risk Factors , United Kingdom
19.
J Med Case Rep ; 4: 232, 2010 Jul 30.
Article in English | MEDLINE | ID: mdl-20673320

ABSTRACT

INTRODUCTION: To the best of our knowledge, this is the first report in the literature of development of neurogenic diabetes insipidus in a patient with subacute liver failure. CASE PRESENTATION: A 25-year-old man presented with subacute liver failure. While awaiting a liver transplant, the patient developed cerebral edema, which resulted in neurogenic diabetes insipidus secondary to cerebral edema. The patient died before the liver transplantation could be carried out. CONCLUSION: Neurogenic diabetes insipidus is well recognized in the neurosurgical population as a consequence of cerebral edema and increased intracranial pressure, both of which occur commonly in patients with subacute liver failure.

20.
J Med Case Rep ; 4: 32, 2010 Jan 30.
Article in English | MEDLINE | ID: mdl-20205844

ABSTRACT

INTRODUCTION: Multicentric Castleman's Disease (MCD), a lymphoproliferative disorder associated with Human Herpes Virus-8 (HHV-8) infection, is increasing in incidence amongst HIV patients. This condition is associated with lymphadenopathy, polyclonal gammopathy, hepato-splenomegaly and systemic symptoms. A number of small studies have demonstrated the efficacy of the anti-CD20 monoclonal antibody, rituximab, in treating this condition. CASE PRESENTATION: We report the case of a 46 year old Zambian woman who presented with pyrexia, diarrhoea and vomiting, confusion, lymphadenopathy, and renal failure. She rapidly developed multiple organ failure following the initiation of treatment of MCD with rituximab. Following admission to intensive care (ICU), she received prompt multi-organ support. After 21 days on the ICU she returned to the haematology medical ward, and was discharged in remission from her disease after 149 days in hospital. CONCLUSION: Rituximab, the efficacy of which has thus far been examined predominantly in patients outside the ICU, in conjunction with extensive organ support was effective treatment for MCD with associated multiple organ failure. There is, to our knowledge, only one other published report of its successful use in an ICU setting, where it was combined with cyclophosphamide, adriamycin and prednisolone. Reports such as ours support the notion that critically unwell patients with HIV and haematological disease can benefit from intensive care.

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