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Biomedical subjects

S Phillips

Publications and source records attributed to S Phillips.

At least 19 recordsLinked to original sources

Practice parameter: diagnostic assessment of the child with status epilepticus (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society.

OBJECTIVE: To review evidence on the assessment of the child with status epilepticus (SE). METHODS: Relevant literature were reviewed, abstracted, and classified. When data were missing, a minimum diagnostic yield was calculated. Recommendations were based on a four-tiered scheme of evidence classification. RESULTS: Laboratory studies (Na(++) or other electrolytes, Ca(++), glucose) were abnormal in approximately 6% and are generally ordered as routine practice. When blood or spinal fluid cultures were done on these children, blood cultures were abnormal in at least 2.5% and a CNS infection was found in at least 12.8%. When antiepileptic drug (AED) levels were ordered in known epileptic children already taking AEDs, the levels were low in 32%. A total of 3.6% of children had evidence of ingestion. When studies for inborn errors of metabolism were done, an abnormality was found in 4.2%. Epileptiform abnormalities occurred in 43% of EEGs of children with SE and helped determine the nature and location of precipitating electroconvulsive events (8% generalized, 16% focal, and 19% both). Abnormalities on neuroimaging studies that may explain the etiology of SE were found in at least 8% of children. RECOMMENDATIONS: Although common clinical practice is that blood cultures and lumbar puncture are obtained if there is a clinical suspicion of a systemic or CNS infection, there are insufficient data to support or refute recommendations as to whether blood cultures or lumbar puncture should be done on a routine basis in children in whom there is no clinical suspicion of a systemic or CNS infection (Level U). AED levels should be considered when a child with treated epilepsy develops SE (Level B). Toxicology studies and metabolic studies for inborn errors of metabolism may be considered in children with SE when there are clinical indicators for concern or when the initial evaluation reveals no etiology (Level C). An EEG may be considered in a child with SE as it may be helpful in determining whether there are focal or generalized epileptiform abnormalities that may guide further testing for the etiology of SE, when there is a suspicion of pseudostatus epilepticus (nonepileptic SE), or nonconvulsive SE, and may guide treatment (Level C). Neuroimaging may be considered after the child with SE has been stabilized if there are clinical indications or if the etiology is unknown (Level C). There is insufficient evidence to support or refute routine neuroimaging in a child presenting with SE (Level U).

Anticonvulsants↗

Artificial neural network is superior to MELD in predicting mortality of patients with end-stage liver disease.

BACKGROUND: Despite its accuracy, the model for end-stage liver disease (MELD), currently adopted to determine the prognosis of patients with liver cirrhosis, guide referral to transplant programmes and prioritise the allocation of donor organs, fails to predict mortality in a considerable proportion of patients. AIMS: To evaluate the possibility to better predict 3-month liver disease-related mortality of patients awaiting liver transplantation using an artificial neural network (ANN). PATIENTS AND METHODS: The ANN was constructed using data from 251 consecutive people with cirrhosis listed for liver transplantation at the Liver Transplant Unit, Bologna, Italy. The ANN was trained to predict 3-month survival on 188 patients, tested on the remaining 63 (internal validation group) unknown by the system and finally on 137 patients listed for liver transplantation at the King's College Hospital, London, UK (external cohort). Predictions of survival obtained with ANN and MELD on the same datasets were compared using areas under receiver-operating characteristic (ROC) curves (AUC). RESULTS: The ANN performed significantly better than MELD both in the internal validation group (AUC = 0.95 v 0.85; p = 0.032) and in the external cohort (AUC = 0.96 v 0.86; p = 0.044). CONCLUSIONS: The ANN measured the mortality risk of patients with cirrhosis more accurately than MELD and could better prioritise liver transplant candidates, thus reducing mortality in the waiting list.

Area Under Curve↗

Two cases of retroperitoneal haematoma caused by interaction between antibiotics and warfarin.

Several commonly prescribed antibiotics are known to interact with warfarin, increasing its anticoagulant effect by different mechanisms. Retroperitoneal bleeding with consequent haematoma is recognised as a complication of over-anticoagulation. Consequences, which are potentially fatal, include hypovolaemic shock and compression of retroperitoneal structures such as the ureter and inferior vena cava.

Aged↗

A Phase I study of the angiogenesis inhibitor SU5416 (semaxanib) in solid tumours, incorporating dynamic contrast MR pharmacodynamic end points.

SU5416 (Z-3-[(2,4-dimethylpyrrol-5-yl)methylidenyl]-2-indolinone; semaxanib) is a small molecule inhibitor of the vascular endothelial growth factor receptor (VEGFR2). A Phase I dose escalation study was performed. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used as a pharmacodynamic assessment tool. In all, 27 patients were recruited. SU5416 was administered twice weekly by fixed rate intravenous infusion. Patients were treated in sequential cohorts of three patients at 48, 65, 85 110 and 145 mg m-2. A further dose level of 190 mg m-2 after a 2-week lead in period at a lower dose was completed; thereafter, the cohort at 145 mg m-2 was expanded. SU5416 showed linear pharmacokinetics to 145 mg m-2 with a large volume of distribution and rapid clearance. A significant degree of interpatient variability was seen. SU5416 was well tolerated, by definition a maximum-tolerated dose was not defined. No reproducible changes were seen in DCE-MRI end points. Serial assessments of VEGF in a cohort of patients treated at 145 mg m-2 did not show a statistically significant treatment-related change. Parallel assessments of the impact of SU5416 on coagulation profiles in six patients showed a transient effect within the fibrinolytic pathway. Clinical experience showed that patients who had breaks of therapy longer than a week could not have treatment reinitiated at a dose of 190 mg m-2 without unacceptable toxicity. The 145 mg m-2 dose level is thus the recommended dose for future study.

Adolescent↗

Prevalence and intensity of intestinal parasitic infections in relation to nutritional status in Mexican schoolchildren.

Undernutrition and intestinal parasitic infections affect childhood development and morbidity in many developing countries. Undernutrition may increase susceptibility to parasitic infections which in turn impair the nutritional status of the host. The relationship between intestinal parasitic infections and nutritional status in 400 Mexican schoolchildren was investigated. More than half of the children in the study showed intestinal parasites and polyparasitism. The prevalence of helminth infections was significantly higher in Oaxaca than in Sinaloa (P < 0.05). Z scores for weight-for-age (WA) and height-for-age (HA) were much lower in children of Oaxaca than in Sinaloa (P < 0.001). A significantly higher Z score for weight-for-height (WH), WA, and HA were found in non-infected versus infected children (P < 0.05). Higher prevalences of intestinal infections were found in children with lower HA and WA than in normally nourished children (P < 0.05). Higher intensities of Ascaris lumbricoides and Trichuris trichiura were found in the schoolchildren of Sinaloa than in Oaxaca (P < 0.01). Negative and significant associations were found between Hymenolepis nana and T. trichiura infection (eggs per gram) and nutritional status. Intestinal parasitic infections may be regarded as main risk factors associated with poor nutritional status in Mexican schoolchildren.

Analysis of Variance↗

Clostridium difficile-associated diarrhoea after internal fixation of intertrochanteric femoral fractures.

The aim of the study presented here was to record the incidence and outcome of Clostridium difficile-associated diarrhoea in patients undergoing surgery for intertrochanteric femoral fractures. Between January 2000 and June 2001, a total of 239 patients who underwent surgery after sustaining an intertrochanteric femoral fracture were included in the study. Seventeen patients developed Clostridium difficile-associated diarrhoea (incidence risk, 7.1%), and six patients died after developing the condition (case fatality rate, 35%). Thus, Clostridium difficile-associated diarrhoea was found to cause significant morbidity and mortality after surgery for intertrochanteric femoral fractures, and antibiotics should be used judiciously in this group of patients.

Age Distribution↗

HIV-specific IgG in cervicovaginal secretions of exposed HIV-uninfected female sexual partners of HIV-infected men.

The presence of human immunodeficiency virus (HIV)-specific antibodies was examined in plasma and cervicovaginal (mucosal) samples of 24 HIV-exposed uninfected (EU) female sexual partners of HIV-infected men, and compared with findings in 18 HIV-infected and 15 low-risk HIV-uninfected women. Only HIV-infected women had detectable HIV-specific immunoglobulin G (IgG) (18 of 18) or HIV-IgA (6 of 18) in cervicovaginal samples by enzyme immunoassay (EIA). However, 3 of 24 EU women had positive Western blot (WB) for HIV-IgG in cervicovaginal secretions, while 2 of 24 EU women and 1 of 15 low-risk controls had indeterminate IgG-WB. EU women with positive or indeterminate IgG-WB in the cervicovaginal samples were similar in risk to the remaining EU women. None of the HIV-uninfected women had mucosal HIV-IgA. The findings suggest that some sexually or parenterally exposed HIV-uninfected women might develop low-level mucosal IgG responses. However, it appears unlikely that HIV-specific cervicovaginal antibodies play a major role in protection from HIV infection in this EU population.

AIDS Serodiagnosis↗

Sirolimus for rescue and primary immunosuppression in transplanted children receiving tacrolimus.

AIMS: The role of sirolimus (SRL) as a rescue agent (n=42) and as a component of primary immunosuppression (n=8) was evaluated in a mixed population of 50 transplanted children receiving tacrolimus (liver: 26, heart: 5, intestinal: 5, liver-intestine: 9, lung: 1, bone marrow: 1, liver-kidney: 1, multivisceral: 1). Rescue indications for tacrolimus (TAC) failure were recurrent acute rejection and acute rejection complicating withdrawal of immunosuppression in posttransplant lymphoproliferative disorder (PTLD). Rescue indications for TAC toxicity were nephrotoxicity, pancreatitis, seizures, hypertrophic cardiomyopathy, and graft-versus-host disease. RESULTS: Mean age at rescue was 11.5 years and mean follow-up was 204 (range 18-800) days. As primary immunosuppression, SRL+TAC prevented early acute rejection in 7/8 children. The indication for rescue resolved in 33/42 children. In children with TAC toxicity, this was associated with decrease in TAC doses by 50%, significant improvements in renal function, and continuing decline in Epstein-Barr virus (EBV) viral load in PTLD patients. Serious adverse events led to discontinuation of SRL in 9/42 rescue patients, 3 of them also experienced acute rejection. Three additional children also experienced acute rejection on SRL therapy (overall incidence 6/50, 12%). Pharmacokinetic analysis in the first week of SRL administration suggested a short half-life (11.8+/-5.5 hr, n=21). CONCLUSIONS: SRL and reduced-dose TAC may achieve adequate immunosuppression without compromising renal function or enhancing EBV viremia significantly.

Acute Disease↗

Opinion statement on the minimal acceptable standards of healthcare in cerebral palsy.

PURPOSE: Recent studies have shown a marked variation in the standards of healthcare for young people with disabilities in different regions of the UK and even within the same health district. Equity in the provision of healthcare is a fundamental principle of the NHS. However, this can only be measured against an agreed minimal standard of healthcare that serves as a benchmark for healthcare purchasers and providers. The aim of the present document is to develop a set of minimum standards of healthcare for children and adults with cerebral palsy (CP). METHODS: The document was developed in two stages by a multi-professional and multi-disciplinary group of practitioners in the field of CP. Initially, members of the panel jointly formulated a statement of what they believed should be the minimal acceptable standards of healthcare in CP drawing on their own experience and the published scientific evidence. In the second stage the views of some of the relevant professional bodies and voluntary organizations on the draft statement were sought. The responses of these organizations were incorporated into the final document if agreed by the panel. RESULTS AND CONCLUSIONS: Twenty-two recommendations were made. These were considered the minimum standards of care in a district general hospital. The emphasis was on the organisation and delivery of healthcare for children with CP. The statement is intended to stimulate debate especially in relation to the equity of service provision throughout the country and may be used to inform purchasers of healthcare. Similarly, it may also be useful to providers of healthcare as an audit tool.

Adult↗

Fomepizole for the treatment of methanol poisoning.

BACKGROUND: Methanol poisoning may result in metabolic acidosis, blindness, and death. The inhibition of alcohol dehydrogenase is fundamental to the treatment of methanol poisoning. We performed a multicenter study to evaluate fomepizole, an inhibitor of alcohol dehydrogenase, in the treatment of patients with methanol poisoning. METHODS: We administered intravenous fomepizole to 11 consecutive patients who presented with methanol poisoning at a participating center. Serial clinical and laboratory studies, including measurements of plasma formic acid and fomepizole, were performed. The outcomes measured were the preservation of visual acuity, the resolution of metabolic acidosis, the inhibition of formic acid production, the achievment of therapeutic plasma concentrations of fomepizole with the dosing regimen, residual illness or disability, and death. RESULTS: Plasma formic acid concentrations were detectable in eight patients, and these concentrations were closely correlated with the initial arterial pH values (r=0.92, P<0.001). In response to fomepizole, plasma formic acid concentrations fell and metabolic abnormalities resolved in all patients. Nine patients survived. Seven patients initially had visual abnormalities, but at the end of the trial no surviving patient had any detectable visual deficits related to methanol poisoning. Fomepizole had few adverse effects. The two patients who died had anoxic brain injury that was present at the time of enrollment. During treatment, methanol had an elimination half-life of 54 hours. CONCLUSIONS: Fomepizole appears to be safe and effective in the treatment of methanol poisoning.

Acidosis↗

Making the links between community structure and individual well-being: community quality of life in Riverdale, Toronto, Canada.

An inquiry into community quality of life was carried out within a framework that recognizes the complex relationship between community structures and individual well-being. Through use of focus groups and key informant interviews, community members, service providers, and elected representatives in a Toronto community considered aspects of their community that affected quality of life. Community members identified strengths of access to amenities, caring and concerned people, community agencies, low-cost housing, and public transportation. Service providers and elected representatives recognized diversity, community agencies and resources, and presence of culturally relevant food stores and services as strengths. At one level, findings were consistent with emerging concepts of social capital. At another level, threats to the community were considered in relation to the hypothesized role neo-liberalism plays in weakening the welfare state.

Community Networks↗

Dissecting hematoma of intracranial internal carotid artery in an 8-year-old girl.

BACKGROUND: An 8-year-old girl had a minor fall without head trauma and she collapsed the following day while playing. She was awake but mute with focal neurologic signs when admitted to hospital. Radiologic imaging studies showed a progressive left cerebral infarct with left hemisphere vascular narrowing and beading. She died on the third hospital day. METHODS: Autopsy including exploration of neck vessels and neuropathological examination was performed. Postmortem studies included immunostaining for immunoglobulins and fixed complement. RESULTS: Subtotal subintimal dissections of both proximal supraclinoid internal carotid arteries were found microscopically. On the left, the subintimal dissection extended into the major branches of the left internal carotid artery as dissecting hematomas with a major compromise of the arterial lumina. Specific IgM deposition at the dissection sites was found. A literature review shows that subintimal dissection of the intracranial internal carotid artery or its branches occurs rarely, it is often fatal, and it is present in patients with a mean age of 17.5 years in cases studied pathologically. Trauma and physical exertion are the most common associated factors. CONCLUSIONS: Among the causes of ischemic stroke in young individuals, dissecting hematomas of the intracranial portions of the internal carotid artery system rank low. Few reported cases have identifiable pre-existing pathology. The pathogenesis of dissecting hematomas in this region is reviewed and expanded with speculation regarding relevant developmental, anatomical, flow stress and possibly humoral factors that are involved in the disruption of the arterial elastica and subsequent development and extension of a subintimal hematoma resulting in luminal closure and often death.

Carotid Artery, Internal↗

The use of outcome measures in physical medicine and rehabilitation within Europe.

The aim of the study was to survey the use of outcome measures in rehabilitation within Europe. It was envisaged that this would provide the basis for further studies on the cross-cultural validity of outcome measures. A postal questionnaire was distributed in November 1998 to 866 units providing rehabilitation. In total, 418 questionnaires were returned, corresponding to a response rate of 48%. These 418 centres treated an estimated 113,000 patients annually, undertaking 360,000 assessments. The survey focused on nine diagnostic groups: hip and knee replacement, low back pain, lower limb amputees, multiple sclerosis, neuromuscular disorders, rheumatoid arthritis, spinal cord lesions, stroke and traumatic brain injury. It identified a relatively small number of dominant outcome assessments for each diagnostic group and some variation in the preference for measures across regions. A large number of measures, however, are being used in one or a small number of locations and with relatively few patients. For rehabilitation of orthopaedic patients the majority of assessments undertaken are at the impairment level. For patients with neurological disorders the emphasis is mostly upon measures of disability.

Amputees↗

Ongoing twin pregnancy after ICSI of PESA-retrieved spermatozoa into in-vitro matured oocytes: case report.

The recovery of immature oocytes from unstimulated ovaries followed by in-vitro maturation (IVM) is an attractive alternative to conventional IVF in the treatment of female infertility. Similarly, surgical recovery of spermatozoa from the epididymis by percutaneous sperm aspiration (PESA) has simplified the retrieval of the male gamete in treatment of men with obstructive azoospermia. We report the first ongoing clinical twin pregnancy resulting from intracytoplasmic sperm injection (ICSI) of spermatozoa retrieved by PESA into IVM oocytes. In the treatment of a 24-year old woman, 12 immature oocytes were retrieved. Six oocytes matured (maturation rate 50%) after 24-hour incubation and were inseminated by ICSI. Four oocytes had two pronuclei (fertilization rate 67%) and 3 good quality embryos were transferred. A viable twin pregnancy was confirmed by ultrasound scan. This report illustrates the use of a combination of less invasive assisted reproductive techniques in overcoming barriers to infertility.

Adult↗

Altered gene profiles in fetal rat testes after in utero exposure to di(n-butyl) phthalate.

Di(n-butyl) phthalate (DBP) has antiandrogenic-like effects on the developing reproductive tract in the male rat and produces regions of interstitial cell hyperplasia and gonocyte degeneration in the developing fetal testes at maternal doses of 100-500 mg/kg/day. Neither DBP nor its primary metabolites interact with the androgen receptor in vitro. The present study was performed to examine gene expression in the fetal rat testes following in utero DBP exposure. Pregnant Sprague-Dawley rats received corn oil, DBP (500 mg/kg/day), or flutamide (reference antiandrogen, 50 mg/kg/day) by gavage daily from gestation day (GD) 12 to 21. Dose levels were selected to maximize fetal response with minimal maternal toxicity. Testes were isolated on GD 16, 19, and 21. Global changes in gene expression were determined by microarray analysis. Selected genes were further examined by quantitative RT-PCR. DBP, but not flutamide, reduced expression of the steroidogenic enzymes cytochrome P450 side chain cleavage, cytochrome P450c17, and steroidogenic acute regulatory protein. Testicular testosterone and androstenedione were decreased on GD 19 and 21, while progesterone was increased on GD 19 in DBP-exposed testes. Testosterone-repressed prostate message-2 (TRPM-2) was upregulated, while c-kit (stem cell factor receptor) mRNA was downregulated following DBP exposure. TRPM-2 and bcl-2 protein staining was elevated in GD 21 DBP-exposed Leydig and Sertoli cells. Results of this study have led to the identification of several possible mechanisms by which DBP can induce its antiandrogenic effects on the developing male reproductive tract without direct interaction with the androgen receptor. Our results suggest that the antiandrogenic effects of DBP are due to decreased testosterone synthesis. In addition, enhanced expression of cell survival proteins such as TRPM-2 and bcl-2 may be involved in DBP-induced Leydig cell hyperplasia, whereas, downregulation of c-kit may play a role in gonocyte degeneration. Future studies will explore the link between these identified gene expression alterations and ultimate adverse responses.

Androgen Antagonists↗