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Biomedical subjects

J Farrar

Publications and source records attributed to J Farrar.

At least 37 records · Page 2Linked to original sources
PubMed2000

Sucrose and the integration of metabolism in vascular plants.

We consider the hypothesis that sucrose is a signal as well as a substrate. We suggest that the significance of sugar sensing in plants is the integration of whole-plant carbon flux so that the capacity of sources to produce sucrose matches the capacity of sinks to consume it. We pay particular attention to difficulties with this hypothesis and the areas where further or better evidence is needed. We conclude that there is strong correlative evidence for a link between sucrose metabolism and the level of expression of key genes, but that a number of different mechanisms may be involved.

Journal Article↗
PubMed2000

Neurological manifestations of dengue infection.

BACKGROUND: Severe forms of dengue, the most important arboviral infection of man, are associated with haemorrhagic disease and a generalised vascular leak syndrome. The importance of dengue as a cause of neurological disease is uncertain. METHODS: During 1995, all patients with suspected CNS infections admitted to a referral hospital in southern Vietnam were investigated by culture, PCR, and antibody measurement in serum and CSF for dengue and other viruses. FINDINGS: Of 378 patients, 16 (4.2%) were infected with dengue viruses, compared with four (1.4%) of 286 hospital controls (odds ratio [95% CI] 3.1 [1.7-5.8]). Five additional dengue positive patients with CNS abnormalities were studied subsequently. No other cause of CNS infection was identified. Seven infections were primary dengue, 13 secondary, and one was not classified. Ten patients had dengue viruses isolated or detected by PCR, and three had dengue antibody in the CSF. 12 of the 21 had no characteristic features of dengue on admission. The most frequent neurological manifestations were reduced consciousness and convulsions. Nine patients had encephalitis. No patient died, but six had neurological sequelae at discharge. Phylogenetic analysis of the four DEN-2 strains isolated mapped them with a DEN-2 strain isolated from a patient with dengue haemorrhagic fever, and with other strains previously isolated in southern Vietnam. INTERPRETATION: In dengue endemic areas patients with encephalitis and encephalopathy should be investigated for this infection, whether or not they have other features of the disease.

Adolescent↗
PubMed1999

Evidence of blood-brain barrier dysfunction in human cerebral malaria.

Patients infected with the malaria parasite Plasmodium falciparum may develop a diffuse reversible encephalopathy, termed cerebral malaria. It is unclear how the intraerythrocytic parasite, which sequesters in the cerebral microvasculature but does not enter the brain parenchyma, induces this neurological syndrome. Adhesion of parasitized red blood cells in the brain microvasculature is mediated by specific receptors on the host endothelium, including intercellular adhesion molecule (ICAM)-1, CD36 and CD31. Leucocyte binding to cerebral endothelial cells in culture induces intracellular signalling via ICAM-1. The hypothesis that parasitized red blood cells binding to receptors on cerebral endothelial cells causes changes in the integrity of the blood-brain barrier was tested. Immunohistochemistry was used to examine the blood-brain barrier in human cerebral malaria, with antibodies to macrophage and endothelial activation markers, intercellular junction proteins, and plasma proteins. The distribution of the cell junction proteins occludin, vinculin and ZO-1 were altered in cerebral malaria cases compared to controls. While fibrinogen was the only plasma protein detected in the perivascular space, there was widespread perivascular macrophage activation, suggesting that these cells had been exposed to plasma proteins. It was concluded that functional changes to the blood-brain barrier occur in cerebral malaria, possibly as a result of the binding of parasitized red blood cells to cerebral endothelial cells. These changes require further examination in vitro.

Adolescent↗
PubMed1999

An outbreak of Salmonella serogroup Saphra due to cantaloupes from Mexico.

An outbreak of Salmonella serogroup Saphra (S. saphra) infections was studied by laboratory-based surveillance, case-control and trace-back studies, and a survey of cantaloupe preparation practices. Twenty-four patients with S. saphra infections had illness onsets between 23 February and 15 May 1997; 75% were </=6 years old; 23% were hospitalized. Case patients were more likely than controls to have consumed cantaloupe (88% vs. 45%; matched odds ratio [MOR], 15. 5; 95% confidence interval [CI], 1.7-139) and precut cantaloupe (59% vs. 19%; MOR, 14.5; 95% CI, 1.6-128). The trace-back study identified 1 growing region in Mexico as the source of cantaloupes for 95% of the patients who ate cantaloupes. Only 17% of case patients washed cantaloupes before cutting them. This outbreak is another example of gastrointestinal disease in the United States associated with imported contaminated produce. Consumers and retailers should wash cantaloupes before cutting them; there should be international efforts to ensure food safety.

Adult↗
PubMed1998

Antibodies affecting ion channel function in acquired neuromyotonia, in seropositive and seronegative myasthenia gravis, and in antibody-mediated arthrogryposis multiplex congenita.

A new autoimmune disease affecting the neuromuscular junction has been defined. Acquired neuromyotonia is associated with antibodies to voltage-gated potassium channels that act, at least in part, by reducing potassium channel function with resulting neuronal hyperactivity. This condition is quite frequently associated with thymoma and, in many cases, antibodies to acetylcholine receptors are present as well as antibodies to VGKC. Improvements in techniques and the availability of cloned DNA and recombinant forms of the AChR subunits have led to new observations concerning the specificity and roles of antibodies in myasthenia gravis. The transfection of a cell line with the epsilon subunit means that we can now accurately compare antibodies reactive with adult and fetal human AChR. This may help to determine the relationship between AChR subunit expression in different tissues and the induction of antibodies that bind specifically to the two forms, as well as to clarify the role of antibodies to fetal or adult AChR in causing ocular muscle symptoms. Serum antibodies from a few mothers with obstetric histories of recurrent arthrogryposis multiplex congenita in their babies specifically inhibit the function of fetal AChR. These observations not only explain the cause of some cases of arthrogryposis multiplex congenita, but also suggest that other fetal-specific antibodies might be responsible for other fetal or neonatal conditions. An animal model has been established to enable us to investigate the role of maternal serum factors in causing such disorders. Seronegative MG has been the subject of many studies from our laboratory over the last ten years. The transience of the effects of SNMG plasmas on AChR function strongly suggests that the plasma antibodies do not bind directly to the AChR, but inhibit function by some indirect mechanism. They do not appear to act via the cAMP-dependent protein kinase pathway, and studies are in progress to investigate the involvement of other second messenger systems.

Adult↗
PubMed1998

Breath testing in patients with respiratory disability.

The presence of chronic respiratory disease is sometimes claimed as a defence by drivers who refuse or fail a breath test. Trials have been conducted with two breath analysis instruments used in the state of Victoria, Australia in order to determine the respiratory parameters compatible with a satisfactory test. Patients with restrictive and obstructive conditions participated in the trial that was conducted in the respiratory unit of a large teaching hospital. The results showed that the evidential breath analyzer currently used in Victoria was able to accept breath samples from subjects at the limit of respiratory function likely to be encountered in drivers. It was also found that a subject capable of providing a breath sample for the current screening device should also be able to provide an evidential sample. The trials provided useful information in evaluating defences of inability to provide a breath sample due to respiratory incapacity.

Journal Article↗
PubMed1998

The effect of blood in the oral cavity on breath alcohol analysis.

The theory that blood (containing alcohol) present in the oral cavity may falsely increase breath analysis recently led to a successful appeal against a drink driving conviction. Subjects who had previously consumed vodka (37.2% alc/vol), at 30 ml/10 kg and reached a BAC (blood alcohol concentration) of between 0.05 and 0.10% were then given four oral solutions consisting of a control (distilled water), and 0.05, 0.10 and 0.15% aqueous alcohol (ethanol) solutions, administered in coded form. A four-way cross-over, blind, randomized assay was conducted with the solutions, with breath analyses conducted in the presence or absence of solution in the mouth. The first trial group (n = 18) received 2 ml of solution, and we found that the simulated 0.15, 0.10 and 0.05% alcohol solutions in the mouth produced BAC reading increases of 0.0088 +/- 0.0014, 0.0062 +/- 0.0008 and 0.0055 +/- 0.0010% respectively (p < 0.001). The second trial group (n = 20) received 1 ml of solution and produced BAC reading increases of 0.0047 +/- 0.0011 (p < 0.001), 0.0023 +/- 0.0008 (p < 0.01) and 0.0020 +/- 0.0006% (p < 0.05) respectively. In conclusion, these studies indicate that small volumes of blood (containing alcohol) in the mouth would not have a practical effect on breath analysis readings.

Clinical Trial↗
PubMed1998

Rapid diagnosis of Japanese encephalitis by using an immunoglobulin M dot enzyme immunoassay.

Japanese encephalitis (JE) occurs in rural settings in southern and eastern Asia, where diagnostic facilities are limited. For the diagnosis of JE virus (JEV) infection, we developed a nitrocellulose membrane-based immunoglobulin M (IgM) capture dot enzyme immunoassay (MAC DOT) that is rapid, simple to use, requires no specialized equipment, and can distinguish JEV from dengue infection. In a prospective field study in southern Vietnam, 155 cerebrospinal fluid (CSF) and 341 serum samples were collected from 111 children and 83 adults with suspected encephalitis. The JEV MAC DOT, performed on site, was scored visually from negative to strongly positive by two observers, and the results were compared subsequently with those of the standard IgM capture enzyme-linked immunosorbent assay. For the 179 patients with adequate specimens, the MAC DOT correctly identified 59 of 60 JEV-positive patients and 118 of 119 JEV-negative patients (sensitivity [95% confidence intervals], 98.3% [92.1 to 99.91%]; specificity, 99.2% [95.9 to 100.0%]; positive predictive value, 0.98; negative predictive value, 0.99). The MAC DOT also correctly identified three patients with dengue encephalopathy. Admission specimens were positive for 73% of JE patients. Interobserver agreement for MAC DOT diagnosis was excellent (kappa = 0.94). The JEV MAC DOT is a simple and reliable rapid diagnostic test for JE in rural hospitals.

Adult↗
PubMed1997

Lack of hepatotoxic effects of parenteral ketorolac in the hospital setting.

BACKGROUND: No large controlled studies to date have examined the hepatic safety of parenteral ketorolac, which is used to treat acutely ill hospitalized patients who may be at greatest risk of liver injury. OBJECTIVE: To measure the association between the use of parenteral ketorolac and subsequent liver injury. METHODS: A nonexperimental cohort study conducted in 35 hospitals in the greater Philadelphia, Pa, region examined 10,272 courses of parenteral ketorolac (the exposed group) and 10,247 courses of parenteral opioid (the comparison group). Liver injury was defined by a modified international consensus definition that relied exclusively on liver function tests. Proportional hazards regression was used to calculate the rate ratio and 95% confidence interval for the association between ketorolac exposure and the occurrence of liver injury, controlling for potentially confounding factors, and to explore the possible effects of duration and dose. RESULTS: The incidence of liver injury was 1.0% in the ketorolac group and 1.2% in the opioid group, yielding an unadjusted rate ratio of 0.77 (95% confidence interval, 0.59 1.01). Simultaneously adjusting for multiple potentially confounding factors did not change this result. There was no evidence for a duration-response relationship (P = .96) or a dose-response relationship (P = .23). We were unable to identify any subgroups that were susceptible to possible hepatotoxic effects of parenteral ketorolac. CONCLUSIONS: This study failed to find evidence of a hepatotoxic effect of parenteral ketorolac use in the hospital setting and provides strong evidence against the existence of a clinically meaningful association between exposure to parenteral ketorolac in the hospital setting and liver injury.

Analgesics, Non-Narcotic↗
PubMed1997

Parenteral ketorolac: the risk for acute renal failure.

BACKGROUND: Acute renal failure has been associated with parenteral ketorolac tromethamine, but the risk that is associated with this therapy has not been quantified. OBJECTIVE: To compare the risk for acute renal failure associated with ketorolac with that associated with opioids. DESIGN: Retrospective cohort study. SETTING: 35 hospitals in or near Philadelphia. PATIENTS: Patients receiving 10,219 courses of parenteral ketorolac and patients receiving 10,145 courses of parenteral opioids. MEASUREMENTS: Acute renal failure was defined by 1) an increase in the serum creatinine concentration of 50% or more and 2) either an absolute increase of 44.2 mumol/L or more for concentrations that were less than 132.6 mumol/L at baseline or an absolute increase of 88.4 mumol/L or more for concentrations that were 132.6 mumol/L or more at baseline. In addition, a secondary definition required a diagnosis by a physician. RESULTS: The overall incidence of acute renal failure was 1.1% after therapy with either ketorolac or opioids. Multivariate-adjusted rate ratios comparing ketorolac with opioids for acute renal failure were 1.09 (95% CI, 0.83 to 1.42) overall, 1.00 (CI, 0.76 to 1.33) for less than 5 days of therapy, and 2.08 (CI, 1.08 to 4.00; P = 0.03) for more than 5 days of therapy. Similar results were obtained when the secondary definition of acute renal failure was used. CONCLUSIONS: Overall, acute renal failure was uncommon in this hospitalized population. Compared with opioids, ketorolac administered for 5 days or less did not increase the rate of renal failure. However, among patients who were treated with analgesics for more than 5 days, ketorolac may be associated with an elevated rate of acute renal failure.

Acute Kidney Injury↗
PubMed1997

Diverse Fab specific for acetylcholine receptor epitopes from a myasthenia gravis thymus combinatorial library.

The muscle weakness in myasthenia gravis (MG) is caused by heterogeneous high-affinity IgG autoantibodies to the nicotinic acetylcholine receptor (AChR), a complex ion channel glycoprotein. These antibodies are clearly responsible for reducing AChR numbers at the neuromuscular junction in myasthenia; however, the origins, diversity, specificity and pathogenicity of individual antibodies have not yet been established. We have cloned and characterized four different AChR-specific Fab from an MG patient's thymus by screening an IgG1/kappa gene combinatorial lambda phage library with soluble human AChR labeled with [125I] alpha-bungarotoxin. Unlike most previously cloned human antibodies, all four Fab immunoprecipitated soluble human muscle AChR. Two Fab strongly inhibited binding of mAb to the main immunogenic region on the alpha subunits and one Fab bound to an epitope on the fetal-specific gamma subunit. In sensitivity and fine specificity, these Fab resembled the anti-AChR antibodies found in many MG patients, including the donor. The closest germline counterparts for their heavy chains were in VH families 1, 3 and 4; however, there were many differences consistent with an antigen-driven response of diverse B cell clones. The combinatorial approach holds promise for further analysis of human autoantibodies.

Adult↗
PubMed1997

Epidemiology and control of egg-associated Salmonella enteritidis in the United States of America.

The isolation rate for Salmonella enterica serotype Enteritidis (SE) in humans in the United States of America (USA) increased from 1,207 sporadic isolates identified in 1976 (0.6 isolates/100,000 population) to 10,201 identified in 1995 (4.0/100,000 population). The proportion of reported Salmonella isolates which were SE increased from 5% to 25% during the same time period. In 1990, 1994, and 1995, SE was the most commonly reported reported Salmonella serotype in the USA. Much of this increase has been associated with the consumption of contaminated shell eggs. An examination of the results of a United States Department of Agriculture (USDA) survey of spent hens at slaughter and unpasteurised liquid egg at breaker plants (liquid egg processors) in 1991 and 1995 reveals an increase in the prevalence of SE isolates overall and in most regions of the USA. SE phage type 4 (pt 4), the predominant SE phage type in other parts of the world, has emerged in the egg industry in the western USA concurrent with a sharp increase in the number of sporadic human SE pt 4 isolates in California and Utah. Research on the molecular structure and virulence of SE pt 4 isolates from the USA as compared with isolates from other parts of the world (human and poultry) should be a priority. A comparison of DNA from pt 4 isolates from the USA and Europe may provide information about the potential threat to public health and poultry in the USA from this phage type. Some regional success in the reduction of human illness as a result of SE control efforts is apparent. The Pennsylvania Egg Quality Assurance Program has shown progress in reducing SE infection in participating flocks. At a national level, however, neither the incidence of human illness due to SE nor the prevalence of SE in flocks and unpasteurised liquid eggs have decreased significantly, despite the implementation of the USDA 'trace back' regulation from 1990 to 1995, and intensified efforts to educate food handlers and to enforce safe food handling practices. More effort is needed to control SE at every stage of the egg continuum, from production through to consumption. A risk-reduction approach, with barriers to the introduction and multiplication of the pathogen throughout the farm-to-table continuum, is the most practical method for reducing human illness from SE in shell eggs at present. An effective long-term solution will require interdisciplinary efforts involving government, industry, consumers, and academics. Interventions should be developed and evaluated in compliance with the potential for reducing the risk to human health and cost-effectiveness.

Animal Husbandry↗
PubMed1993

Intra-arterial streptokinase in acute ischaemic stroke. A pilot study.

AIMS: To assess the safety and efficacy of the intra-arterial administration of streptokinase within 24 hours of acute ischaemic stroke. METHODS: Patients who presented to the Austin Hospital casualty department between 3 and 22 hours after an acute stroke were considered for the study. Eligible patients had pretreatment non-contrast computed tomographic scans of the brain to exclude haemorrhage. Streptokinase (250,000 units) was administered directly into the common carotid artery or the cervical portion of the internal carotid artery. MAIN OUTCOME MEASURES: The incidence of symptomatic and asymptomatic cerebral haemorrhage, haemorrhagic transformation of infarction, angiographic reperfusion, clinical outcome at seven to 10 days and the frequency of other complications. RESULTS: Thirteen patients were treated over a 16-month period. Major clinical improvement occurred in five patients (39%) at 48 hours. This was associated with angiographically demonstrated recanalisation of a middle cerebral artery occlusion in two patients and partial recanalisation in two others. Significant hypotension in two patients required therapy to be stopped. In five other cases mild hypotension developed but the streptokinase infusion was completed. Haemorrhagic transformation of the infarct occurred in four patients without clinical deterioration. CONCLUSION: Intra-arterial administration of streptokinase is safe in selected patients with acute ischaemic stroke. The theoretical benefit of an increased local thrombolytic effect and reduced systemic complications, compared with the use of higher intravenous doses, justifies a randomised clinical trial. If therapies such as this are to be successful, rapid referral to an appropriate centre is necessary.

Aged↗