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Biomedical subjects

R Harrison

Publications and source records attributed to R Harrison.

At least 91 records · Page 5Linked to original sources

Sepsis-induced depression of rat glucose-6-phosphatase gene expression and activity.

Sepsis in rats decreases the hepatic expression of the gluconeogenic enzyme glucose-6-phosphatase (G6Pase). The aim of this study was to investigate the relationship among G6Pase transcription, mRNA, enzymatic activity, and serum glucose levels at different intervals during mild or fulminant sepsis. Both fulminant and mild sepsis immediately decreased hepatic G6Pase mRNA levels. In mild sepsis, levels began to recover late in the time course. Serum glucose levels were maintained in mild sepsis but decreased markedly in fulminant sepsis. G6Pase transcription after fulminant sepsis decreased and never recovered. A similar transcriptional decrease was noted in mild sepsis, but some recovery occurred in this state. Histochemistry after mild sepsis revealed a decrease in G6Pase protein and enzymatic activity that paralleled transcription. These studies suggest that changes in G6Pase transcription and activity are early markers for sepsis-induced alterations in hepatic function. Mechanisms other than gene expression and enzymatic activity serve to maintain glucose levels in mild sepsis, but in the fulminant disorder, compensatory mechanisms fail and hypoglycemia develops.

Animals↗

Schistosoma mansoni antigens applicable to diagnosis of prepatent infections.

Diagnosis of schistosomiasis still depends upon demonstration of eggs in excreta, by which time significant pathology may occur to the human host. This study was undertaken to identify Schistosoma mansoni antigen(s) to be exploited in serodiagnosis of prepatent and/or acute infections. Immunoglobulin G and M responses of inbred and outbed mice to Schistosoma mansoni whole adult worm antigen were monitored in immunoblots using sera obtained at sequential times from mice infected with either 600 or 100 Schistosoma mansoni cercariae each. Regardless of the initial infection dose, immunoblot reactions to two doublets, 31/32 and 34/35 kDa appeared as early as two and three weeks post infection respectively and reactions to 38 and 70 kDa antigens appeared after five weeks infection. Antigens 31/32 and 38 induced both IgG and IgM responses whereas 34/35 and 70 predominantly induced IgG response. Homologues of these four antigens equally reactive with serum of infected mice were also demonstrated in Schistosoma haematobium, worms. Examination of sera from 25 patients suffering from acute Schistosoma mansoni, two suffering from Schistosoma haematobium and 16 patients suffering from infections with other parasite species confirmed the potential of 31/32, 34/35 and 38 kDa antigens in the specific diagnosis of prepatent and acute schistosomal infections but showed cross-reactivity of the 70 kDa antigen.

Adolescent↗

Can telemedicine be used to improve communication between primary and secondary care?

OBJECTIVE: To test feasibility and acceptability of teleconferencing routine outpatient consultations. DESIGN: Exploratory trial of teleconferenced outpatient referrals of general practitioners. SETTING: An inner city teaching hospital and surrounding general practices. SUBJECTS: Six general practices linked to hospital outpatient clinics. MAIN OUTCOME MEASURES: Levels of participants' satisfaction measured with self administered questionnaires. RESULTS: 54 teleconsultations were performed in 10 different specialties. Few serious technical problems were encountered, and high levels of satisfaction with the consultations were reported by patients, hospital specialists, and general practitioners. CONCLUSIONS: Teleconferenced consultations for routine outpatient referrals with joint participation of general practitioner were feasible. These may have an important potential benefit for improving communication between primary and secondary care.

Ambulatory Care↗

Continuous arterial gas monitoring: initial experience with the Paratrend 7 in children.

OBJECTIVE: To describe clinical usage of the Paratrend 7 continuous arterial blood gas monitor in children. DESIGN: Children older than 24 months of age who required significant ventilatory intervention were eligible for sensor placement. INTERVENTIONS: The sensor was placed via the arterial catheter to measure pH, PCO2, PO2, and temperature. The simultaneous arterial blood gas value was recorded along with the sensor reading. RESULTS: The sensor functioned for as long as seven days and provided the clinicians with data on the patient's respiratory status. The statistical validity of the device when compared to the arterial blood gas showed that the bias/precision for pH was 0.006/0.024, for PCO2 -0.78/4.68 mmHg, and for PO2 1.9%/17.1% (mmHg). CONCLUSIONS: This report demonstrates actual clinical use of continuous blood gas monitoring in children. The information obtained is a major asset to the management of critically ill children in the intensive care unit.

Age Factors↗

Determination of half-reaction equilibrium in a ping-pong enzyme mechanism.

Substituted enzyme (or ping-pong) mechanisms usually involve enzymes that exist in two forms that alternate during the catalytic reaction. A method is described here for determining the position of the equilibrium of a half reaction in a ping-pong enzyme mechanism that is based on the kinetics of the burst reaction which occurs upon addition of reactants that recycle the enzyme from one form to another. The theoretical basis for the analysis is developed, and the method is applied to the half reaction of the aldimine form of aspartate transaminase with difluoro-oxaloacetate.

Animals↗

Genotypic analysis of infant macaques infected transplacentally and orally.

The SIV-infected macaque provides an excellent model to study factors involved in maternal-fetal transmission of HIV. In our prenatal transmission studies, female macaques were inoculated intravenously during midgestation with either SIV/DeltaB670 or a combination of SIV/ DeltaB670 and the macrophage-tropic molecular clone SIV/17E-Fr. The females harbored a genetically diverse virus population at parturition, whereas a single genotype from the maternal quasispecies was identified in the infants. One of two variants was transplacentally transmitted to the infants, SIV/17E-Fr or B670-Cl 12, a genotype contained within the SIV/ DeltaB670 inoculum. Both of these variants have been identified in the central nervous system of macaques that have developed encephalitis and they replicate in vitro on primary rhesus macrophages. These results suggest a critical role for macrophages in fetal infection in utero. In our perinatal transmission studies we have evaluated the viral genotypes found in two newborn macaques infected orally with SIV/DeltaB670 and in one infant infected via amniotic inoculation in late gestation. More than one viral genotype was identified in each infant, moreover, each infant harbored different genotypes. These results suggest different mechanisms are responsible for viral infection via these routes.

Amino Acid Sequence↗

Risk factors for liver rejection: evidence to suggest enhanced allograft tolerance in infancy.

After liver transplantation, a relatively low intensity immunosuppressive regimen is employed in our unit: after initial triple therapy (prednisolone, azathioprine, cyclosporin), prednisolone is discontinued at three months and azathioprine at one year. A retrospective study was therefore performed to determine the incidence of rejection, and to identify risk factors for rejection in our patient population. Over a 10 year period, 135 transplants were performed on 109 children. Thirty four (25%) were on infants less than 1 year old. Incidences of acute rejection and irreversible chronic rejection were calculated for grafts surviving more than one and four weeks respectively. Acute rejection occurred in 51 of 101 allografts (50%), and irreversible chronic rejection in 11 of 91 allografts (12%). The immunosuppression strategy was not associated with an increased incidence of rejection. Acute rejection occurred in only eight of 28 allografts (29%) in those transplanted during their first year, compared with 43 of 73 (59%) in older children. Logistic and Cox regression analysis supported age at transplantation as a significant risk factor for acute rejection. Irreversible chronic rejection did not occur in any of 24 grafts in patients transplanted before one year, compared with 11 of 67 (16%) in older recipients. This suggests possible enhanced allograft tolerance with transplantation during the first year of life. This unexpected and potentially important finding now requires confirmation in other large patient series, with blind interpretation of post-transplant liver biopsies.

Adolescent↗

Increased expression of cytokine-induced neutrophil chemoattractant in septic rat liver.

Hepatocellular dysfunction in sepsis may be neutrophil mediated. We therefore tested the hypothesis that sepsis-induced neutrophil accumulation is associated with increased expression of the chemokine, cytokine-induced neutrophil chemoattractant (CINC). In Sprague-Dawley rats made septic by cecal ligation and puncture, we demonstrate a time-dependent increase in CINC mRNA, which returns to baseline by 48 h. By in situ hybridization, this mRNA is present in hepatocytes and nonparenchymal cells. CINC protein levels in septic animals parallel mRNA levels and resolve by 48 h. Because CINC expression is induced by cytokines including tumor necrosis factor-alpha (TNF- alpha), we show, by immunohistochemistry, that sepsis elevates intrahepatic TNF-alpha. Finally, because the CINC promoter is transactivated by the transcription factor, nuclear factor kappa B (NF-kappa B), we determined that hepatic NF-kappa B DNA binding increases dramatically, peaking 16 h after cecal ligation and puncture. Thus activated NF-kappa B may mediate CINC induction in sepsis. This constellation of findings suggests a mechanism by which sepsis may induce neutrophil accumulation in the liver and may have implications regarding sepsis-induced hepatic dysfunction.

Animals↗

The future role of telemedicine at the interface between primary and secondary care.

Telemedicine has been in existence for 25 years. Owing to the primitive state of technological development and poor telecommunications, early projects could not be sustained. Recent improvements in technology and communications, together with a convergence of political and economic trends, has led to a massive surge in development. In the UK one promising application is to link GPs with hospital specialists. This offers the potential for improved quality of communication, more effective use of expensive resources, and more convenient delivery of medical services to the patient.

Evaluation Studies as Topic↗

Motor evoked potential monitoring during spinal surgery: responses of distal limb muscles to transcranial cortical stimulation with pulse trains.

During spinal surgery, motor evoked potentials (MEPs) were recorded from distal upper and lower limb muscles following multipulse transcranial electrical stimulation of the cortex. Twenty-two patients, 9 of them myelopathic, were anaesthetised with propofol +/- nitrous oxide. Using trains of 3-6 pulses separated by 2 ms, consistent responses generally measuring more than 100 microV were obtained from every patient except one, and persisted with nitrous oxide concentrations as high as 74%. Responses could usually be elicited from 3 or more limbs simultaneously, although the location of the stimulating anode was sometimes critical. The lower limb responses of one patient disappeared transiently during excision of an intramedullary tumour; his leg weakness was increased for a few days after surgery. Three other patients experienced increased weakness or spasticity, two without concomitant MEP changes and one with no recordable responses. Although other methods may be preferable in some circumstances, we believe this represents an advance over previously reported non-invasive techniques for peroperative MEP monitoring, and may be particularly useful for monitoring patients with myelopathy in the thoracic region.

Adult↗

Molecular activation-deactivation of xanthine oxidase in human milk.

Enzymic activity and protein levels of xanthine oxidase were measured in serial samples of breast milk donated by each of 14 mothers, starting, in all but two cases, within 7 days following parturition. Enzyme activity varied widely, usually reaching peak values during the first 15 days and falling thereafter, by as much as 98%, to basal levels that were subsequently largely maintained. Corresponding changes in xanthine oxidase protein levels were not observed and, consequently, the specific activity of xanthine oxidase followed the above pattern. The capacity of human xanthine oxidase to undergo activation-deactivation cycles at the molecular level has important implications, not only for its role in breast milk, but also for its potential as a source of reactive oxygen species in other human tissues.

Enzyme Activation↗

Outbreak of Salmonella enteritidis phage type 4 infection associated with cheese and onion quiche.

Twelve people developed gastrointestinal symptoms suggestive of food poisoning after a party attended by between 60 and 80 people. The outbreak went unrecognised, however, until general practitioners admitted three patients to hospital, where faecal specimens were examined. An epidemiological investigation identified 12 cases, and a case control study showed a significant association between illness and eating a cheese and onion quiche at the party. Salmonella enteritidis phage type 4 was cultured from three out of seven faecal specimens obtained from cases. Consultants in communicable disease control should continue to encourage general practitioners to investigate and notify suspected cases of food poisoning.

Adult↗