Search PubMed⌕ Search

Biomedical subjects

S Harris

Publications and source records attributed to S Harris.

At least 91 records · Page 5Linked to original sources
PubMed1999

Attitudes to organ donation among South Asians in an English high street.

In the UK, people of South Asian origin are at more than twice the risk of end-stage renal failure encountered in the Caucasian population but are under-represented among organ donors. Difficulties with matching mean that few donated kidneys are suitable for transplantation to South Asian recipients. A survey of attitudes in 100 South Asian adults was conducted in the main street of Southall, Middlesex. 90 of those questioned were aware of organ transplantation and 69 had heard about donor cards. However, the 16% who carried a donor card was lower than the 28% reported in the general population. The main reason for the low organ donation rate by South Asians seemed to be lack of knowledge, and this could be remedied by more targeting of information in the Asian media.

Adolescent↗
PubMed1999

Social conditions and paediatric day case tonsillectomy.

OBJECTIVE: To develop a simple method for assessing the proportion of children referred to hospital for tonsillectomy in different areas likely to be suitable for day case treatment based on their medical and social characteristics. METHODS: Four patient suitability criteria were selected based on previous experience of successful day case surgery and a literature review of the prevalence of contraindications and postoperative complications, as follows: medical contraindications (at least American Society of Anesthetists grade ASA2 to be eligible); home circumstances (no telephone, no car and single parent households were ineligible); distance from the hospital (more than 10 miles resulted in ineligibility); and likelihood of postoperative complications. Data relating to the social criteria were collected prospectively from 500 children under 12 years of age reviewed in the outpatient department and under the care of one of the authors. In addition, the electoral ward UPA8 (Jarman 8) deprivation score relevant to each child was recorded and the sample was divided into quintiles according to mean UPA8 scores. In each quintile, the percentage of children with the appropriate social criteria for day case tonsillectomy was calculated. The relationship between deprivation score and social criteria for day case tonsillectomy was determined using logistic regression. RESULTS: The proportion of children deemed socially suitable for day surgery fell continuously from 95% in the least deprived quintile to 55% in the most deprived group (proportion passing the social criteria for suitability = -1.5035 + 0.0298UPA8). Using these findings and those from the literature review on the nature and prevalence of contraindications and postoperative complications, a simple formula for realistic day case tonsillectomy targets was specified as A x B x C x D x 100%, where A is the proportion of children with no additional medical problems, B is the proportion passing the social suitability criteria, C is the proportion living within 10 miles and D is the proportion with no postoperative complications. Values for A and D would be derived from local audits. CONCLUSIONS: The formula can be used by purchasers and hospital managers to set differential day case targets for hospitals related to the characteristics of their patients referred for tonsillectomy. In principle, a similar approach could be applicable to other procedures and other age groups.

Ambulatory Surgical Procedures↗
PubMed1998

Potential fitness benefits of group living in the red fox, Vulpes vulpes.

For species such as the red fox, spatio-temporal variation in resource availability may promote group living even when the benefits of group formation are not of significant magnitude to promote territorial expansion and delayed dispersal. In this paper we use data from an urban fox population to compare the relative benefits of dispersal and natal philopatry as routes to attaining dominant status and investigate the potential benefits of territory inheritance, alloparental care and reproduction to subdominant individuals. More offspring, of either sex, remained on their natal territory than dispersed. The annual rate of retention of dominant status and the annual mortality rate of subdominant animals was high, such that the majority of subdominant animals never became dominant. The mortality rate of dispersing individuals was also high. The relative success rate of dispersal and philopatry as routes to dominance were broadly similar, although several philopatric offspring became dominant only after their natal territory was divided: in the absence of such changes, dispersal was more likely to lead to dominant status. Thus, it is likely that some other benefit was accrued by philopatric individuals. The majority of subdominants provisioned cubs. This did not increase the number of cubs reared but reduced the level of provisioning by dominants: whether this promoted dominants' longevity is unknown. There were high levels of reproduction by subordinate females and the levels of alloparental care by subdominants of both sexes suggest that there are comparable levels of direct reproduction by subdominant males. (c) 1998 The Association for the Study of Animal Behaviour.

Journal Article↗
PubMed1998

An autoantibody is modified for use as a delivery system to target the cell nucleus: therapeutic implications.

A murine monoclonal anti-dsDNA antibody was found to penetrate living cells and localize in the nucleus without pathologic effects. A single mutation in VH markedly enhanced cellular penetration. The mutant antibody was produced as recombinant Fab and single chain antibody fragments to investigate its use as a delivery system to target the cell nucleus. Complexes were made containing Fab fragments and alkaline phosphatase conjugated goat antibodies to mouse |gk chains. Fab fragments transported 305 kDa goat antibody-enzyme complexes into the nucleus in COS-7 and CHO cells. A single chain antibody cDNA was constructed by splice overlap extension PCR and expressed in COS-7 cells. Binding of the single chain antibody to dsDNA was shown by ELISA, and cellular penetration and nuclear localization were demonstrated in COS-7 and CHO cells. The single chain antibody cDNA was ligated into the expression vector, pEGFP, to produce a fusion protein with green fluorescent protein. The fusion protein penetrated COS-7 cells and localized in the cell nucleus. The single chain antibody produced during sustained expression in CHO cells re-entered antibody-producing cells and localized in the nucleus without affecting cell viability. Our results demonstrate the potential use of a modified autoantibody as a delivery system to target the cell nucleus.

Animals↗
PubMed1998

Cartilage protective agent (CPA) Ro 32-3555, a new matrix metalloproteinase inhibitor for the treatment of rheumatoid arthritis.

CPA was well tolerated at all dose levels (10-150 mg) following single oral dose administration to healthy male volunteers. There was no relationship between the intensity, duration and number of adverse events reported and the dose of CPA. There was a dose-related increase in exposure as measured by AUC0-infinity and Cmax. Administration of 10 mg CPA following food resulted in a delayed tmax, and a significant decrease in Cmax but not AUC0-infinity.

Adult↗
PubMed1998

Renal tract abnormalities detected in Australian preschool children.

OBJECTIVE: To quantify the incidence of abnormalities in urinalysis and blood pressure from preschool children and their predictive value in detecting renal disease within an Australian community. METHODOLOGY: Urine samples, blood pressure and height measurements and parental reports of significant medical problems were collected from a total of 9355 South Australian preschool children. Seven hundred and forty-three children with abnormal results were investigated in a nephrology outpatient clinic. A control group of 357 children with no detectable abnormality were also recalled, examined and, where appropriate, investigated. RESULTS: Nine thousand, three hundred and fifty-five children were tested. Of these, 0.81% were shown to have a clinically significant renal tract abnormality. The findings included children with urinary tract infections, vesico-ureteric reflux, glomerular disease, renal calculi, essential hypertension and a renal neoplasm. While dipstick-based methods were the most specific indicators of renal tract abnormalities, measurement of blood pressure and urinary beta2-microglobulin were also important in detecting abnormalities. Screening for glycosuria did not result in the detection of significant undiagnosed abnormalities. In the control group with no abnormality detected at testing, there was one case each of aortic coarctation, polycystic kidney disease and vesico-ureteric reflux diagnosed. CONCLUSION: Undiagnosed renal tract abnormalities are present in many Australian preschool children. Most are detectable by a thorough history, examination and urinalysis.

Blood Pressure Determination↗
PubMed1997

Fertility control as a means of controlling bovine tuberculosis in badger (Meles meles) populations in south-west England: predictions from a spatial stochastic simulation model.

A spatial stochastic simulation model was used to assess the potential of fertility control, based on a yet-to-be-developed oral bait-delivered contraceptive directed at females, for the control of bovine tuberculosis in badger populations in south-west England. The contraceptive had a lifelong effect so that females rendered sterile in any particular year remained so for the rest of their lives. The efficacy of fertility control alone repeated annually for varying periods of time was compared with a single culling operation and integrated control involving an initial single cull followed by annually repeated fertility control. With fertility control alone, in no instance was the disease eradicated completely while a viable badger population (mean group size of at least one individual) was still maintained. Near eradication of the disease (less than 1% prevalence) combined with the survival of a minimum viable badger population was only achieved under a very limited set of conditions, either with high efficiency of control (95%) over a short time period (1-3 years) or a low efficiency of control (20%) over an intermediate time period (10-20 years). Under these conditions, it took more than 20 years for the disease to decline to such low levels. A single cull of 80% efficiency succeeded in near eradication of the disease (below 1% prevalence) after a period of 6-8 years, while still maintaining a viable badger population. Integrated strategies reduced disease prevalence more rapidly and to lower levels than culling alone, although the mean badger group size following the onset of control was smaller. Under certain integrated strategies, principally where a high initial cull (80%) was followed by fertility control over a short (1-3 year) time period, the disease could be completely eradicated while a viable badger population was maintained. However, even under the most favourable conditions of integrated control, it took on average more than 12 years following the onset of control for the disease to disappear completely from the badger population. These results show that whilst fertility control would not be a successful strategy for the control of bovine tuberculosis in badgers if used alone, it could be effective if used with culling as part of an integrated strategy. This type of integrated strategy is likely to be more effective in terms of disease eradication than a strategy employing culling alone. However, the high cost of developing a suitable fertility control agent, combined with the welfare and conservation implications, are significant factors which should be taken into account when considering its possible use as a means of controlling bovine tuberculosis in badger populations in the UK.

Animals↗
PubMed1997

Running exercise may reduce risk for lung and liver cancer by inducing activity of antioxidant and phase II enzymes.

The effects of exercise, ethanol, and exercise plus ethanol-treatments on activity of superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST) and UDP-glucuronosyl transferase (UDP-GT) in lung and liver were investigated. All treatments induced SOD and CAT activity in the lung while CAT activity was enhanced only by the combined treatments in the liver. Ethanol reduced hepatic SOD activity, while with the combined treatment SOD was normal. Exercise enhanced UDP-GT activity in liver and lung while ethanol had no effect and GST activity was induced in the liver by the combined treatment. Thus exercise may reduce risk for lung and hepatic cancer and prevent an ethanol-induced increase in risk for hepatic cancer by enhancing activity of antioxidant and phase II enzymes.

Animals↗
PubMed1997

Pulmonary surfactant protein SP-B interacts similarly with dipalmitoylphosphatidylglycerol and dipalmitoylphosphatidylcholine in phosphatidylcholine/phosphatidylglycerol mixtures.

Porcine pulmonary surfactant-associated protein SP-B was incorporated into bilayers of chain-perdeuterated dipalmitoylphosphatidylglycerol (DPPG-d62) and into bilayers containing 70 mol % dipalmitoylphosphatidylcholine (DPPC) and 30 mol % DPPG-d62 or 70 mol % chain-perdeuterated DPPC (DPPC-d62) and 30 mol % DPPG. The effect of SP-B on the phase behavior, lipid chain order, and dynamics in these bilayers was examined using deuterium nuclear magnetic resonance (2H-NMR). In both DPPG-d62 and the mixed lipid system, SP-B is found to have little effect on chain order in the liquid crystalline phase. With 11% (w/w) SP-B present, both bilayer systems display a continuous change from liquid crystal to gel with no evidence of two-phase coexistence near the transition. Despite its limited effect on chain order in these bilayers, SP-B is found to strongly perturb chain deuteron transverse relaxation in the liquid crystal and gel phases of DPPG-d62 and the DPPC/DPPG (7:3) mixtures. The observation that SP-B associates with the bilayer in a way which substantially alters the slow motions responsible for transverse relaxation without significantly affecting chain order in either the liquid crystal or gel phases may place some constraints on possible models for that association.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1997

Effects of human tumor cell lines on local new bone formation in vivo.

Although some tumors cause osteolytic lesions, there are some that stimulate new bone formation. This is an important phenomenon because the responsible mechanisms probably represent an aberration of normal physiological bone formation, and identifying the factors involved in the process may lead to new therapies for various bone diseases. To clarify our understanding of the potential mechanism responsible, we compared and quantitated the extent of new bone formation stimulated by human tumors (HeLa, Hep-2, AV-3, FL, WISH and KB), some of which have osteogenic activity in vivo [2]. Tumor cells were injected over the calvaria of nude mice to examine formation of new bone. The tumor cells produced three histologically distinct patterns of new bone growth: (1) WISH and KB stimulated appositional bone growth adjacent to periosteal bone surfaces; (2) HeLa and Hep2 induced new bone growth over calvarial surface even when distant from the tumor mass; (3) FL stimulated bone formation adjacent to periosteum as well as ectopic bone formation in sites distant from bone. All tumors except AV3 induced mean new bone thickness >100 microm, and Hep-2 cells produced bone 330 microm thick. PCR and Northern blot analysis of mRNA isolated from cultured tumor cells revealed that all cell lines expressed mRNA for TGFbeta, (fibroblast growth factor) FGF-1, FGF-2, and IGF-I, and most cell lines produced mRNA for PDGF. Only FL expressed large amounts of mRNA for BMP2. In serum-free conditioned media from Hep2 and HeLa cells purified by heparin affinity chromatography, we have identified FGF-I, FGF-2, and PDGF by immunodetection with specific antibodies. Our results show that new bone growth caused by these tumors is likely due to the production of bone growth factors by the tumor cells, and that the overall effects on bone may be due to several factors working in concert.

Animals↗
PubMed1997

Recurrent Streptococcus pneumoniae sepsis in children with sickle cell disease.

Streptococcus pneumoniae sepsis is the most common invasive infection among patients with sickle cell disease. The risk of a recurrent episode of sepsis and subsequent death in those patients who have had a previous septic event is much higher. Patients with sickle disease who have had pneumococcal sepsis should continue penicillin prophylaxis indefinitely and should not be candidates for out-patient management of febrile episodes.

Anemia, Sickle Cell↗
PubMed1997

Effects of farm management practices on cattle grazing behaviour and the potential for transmission of bovine tuberculosis from badgers to cattle.

Despite the large body of circumstantial evidence to suggest a link, the means by which bovine tuberculosis is passed from badgers to cattle remains unclear; pasture contamination with the urine, faeces and/or sputum of infectious badgers is believed to be the main route of transmission. Therefore the behaviour of grazing cattle was studied to determine whether they avoided investigating and/or grazing pasture contaminated with badger excreta, and whether different farm management practices enhanced the potential for disease transmission. Active latrines were avoided by most cattle until the sward length in the rest of the field was reduced, after which there was an increasing likelihood that active badger latrines would be grazed. Most of the cattle grazed active badger latrines, but cattle of low rank within the herd grazed latrines more heavily. Farm management practices that reduced the availability of long swards shortened the period of investigative behaviour and greatly enhanced the risk that cattle would graze active badger latrines. Cattle were more likely to graze pasture away from latrines that was contaminated either with badger urine or single faeces. Because bacilli remain viable in the soil for up to 2 years, there is the potential for bacilli to accumulate at active badger latrines, and these could pose a significant risk to cattle, even when the latrine is no longer being used by badgers. Cattle readily grazed the lush sward at disused latrines, during which they could ingest contaminated soil; the amount of soil ingested increases as sward length decreases.

Animal Feed↗
PubMed1997

pPV: a novel IRES-containing vector to facilitate plasmid immunization and antibody response characterization.

BACKGROUND: The ability to derive immunological reagents for basic and applied research in a timely fashion is a basic requirement of many research projects and is becoming increasingly important as the number of novel gene products of potential interest continues to evolve rapidly. DNA immunization provides a means of facilitating the production of antibody reagents by circumventing the need to derive either purified protein or define peptides before initiating an in vivo immunization protocol. OBJECTIVES: The DNA construct pPV, for plasmid vaccination, has been designed to facilitate the generation and characterization of antibody reagents against either random or defined molecular targets. STUDY DESIGN: pPV incorporates mammalian regulatory and structural features that promote expression of a bifunctional messenger RNA (mRNA) from a single promoter within mammalian cells both in vitro and in vivo. The bifunctional mRNA encodes a control epitope (human IL5), and the 'test' epitope expressed as a tagged recombinant polypeptide in either a random 'shot-gun' mode or a predetermined fashion. In addition, to aid subsequent characterization of antibody responses elicited in vivo, a T7 promoter is included to enable in vitro expression of tagged recombinant polypeptides. RESULTS: The utility and functionality of pPV for the in vitro expression of recombinant protein and the in vivo elicitation of antibody responses is illustrated using a defined 'test' epitope, human proIL1 beta. CONCLUSION: It is anticipated pPV will find particular utility in the future rapid generation and characterization of antibody reagents against the plethora of novel genes emerging from ongoing genomics activity in a directed or genome wide fashion.

Amino Acid Sequence↗
PubMed1997

Evaluation of indapamide 1.25 mg once daily in elderly patients with mild to moderate hypertension.

The objective of this study was to evaluate the safety and efficacy of indapamide 1.25 mg once daily as monotherapy in elderly patients (65 years and older) with mild to moderate essential hypertension. Two hundred and seventy-nine (279) elderly patients were enrolled in a washout period, during which patients received single-blind placebo for 4 weeks. Patients demonstrating supine diastolic pressures between 95 mm Hg and 114 mm Hg at the end of the 4-week placebo washout period were entered into the 8-week double-blind treatment period. Two hundred and four (204) patients qualified for the study and were randomized to the double-blind treatment; 103 patients received indapamide 1.25 mg and 101 patients received placebo for 8 weeks. Overall, 177 patients (92 indapamide and 85 placebo) completed the study. The primary efficacy criterion was the mean change in supine diastolic blood pressure (DBP) from double-blind baseline to the end of 8 weeks of therapy. By week 8 of the double-blind treatment period, indapamide 1.25 mg produced a statistically significant (P = 0.0037) decrease in supine DBP of 8.2 mm Hg compared to a decrease of 5.3 mm Hg produced in the placebo group. Additionally, indapamide 1.25 mg was statistically (P = 0.0028) more effective than placebo in reducing supine systolic BP (SBP) (-10.1 vs -4.2 mm Hg). The incidence of drug-related adverse events during the double-blind treatment period was similar between the two treatment groups. A low dose of indapamide, 1.25 mg, given once daily for 8 weeks was effective as monotherapy with respect to BP reduction in an elderly population with mild to moderate hypertension. Indapamide 1.25 mg was safe and generally well tolerated in this elderly patient population.

Aged↗
PubMed1997

JSJ-1, an anti-spermidine monoclonal antibody with potential clinical applications.

Polyamines have been implicated in a wide variety of functions including nucleic acid synthesis and protein synthesis. Their levels have been shown to increase in response to cell growth and differentiation. Use of polyamines as prognostic indicators of proliferative disease conditions has been hindered by the lack of suitable rapid and sensitive assays. We report the characterization of an anti-spermidine antibody, JSJ-1, with novel putrescine cross reactivity. JSJ-1 cross-reacts more strongly with putrescine (11%) than with spermine (6%). This suggests that the aminobutyl group common to both putrescine and spermidine is an important element in the antibody-antigen interaction. We have demonstrated that antibody-spermidine binding is effected by increased ionic strength. This finding is consistent with the antibody-antigen interaction being ionic. The JSJ-1 antibody has been successfully used to detect increased polyamine levels in clinical serum samples and identify those with increased polyamine levels.

Animals↗
PubMed1997

Factors affecting the pharmacokinetics of parenteral chloramphenicol in enteric fever.

Chloramphenicol pharmacokinetics were studied in 29 Nepalese adults diagnosed with uncomplicated enteric fever and randomized to receive succinate ester 30 mg/kg i.v. or i.m. Serial plasma concentrations of chloramphenicol, and iothalamate (to estimate glomerular filtration rate), antipyrine (hepatocellular function) and Indocyanine Green (liver blood flow) were measured by HPLC and kinetic parameters estimated by non-compartmental analysis. In culture-positive patients (n = 16), mean residence times (MRTs) and steady-state volumes of distribution (V(d)ss) for i.v. chloramphenicol (mean +/- S.D.; 4.9 +/- 0.9 h and 1.9 +/- 0.8 L/kg; n = 7) were less than after i.m. chloramphenicol (12.3 +/- 7.3 h and 3.7 +/- 2.5 L/kg; n = 9; P < 0.05), with a higher peak plasma concentration after i.v. (16.2 +/- 9.1 versus 7.8 +/- 3.6 mg/L; P < 0.05); plasma clearance (Cl(p)) was similar in the two groups (368 +/- 172 and 310 +/- 224 mL/kg/min after i.v. and i.m. respectively). In 17 patients examined during convalescence, MRT and Vdss were less than in acute illness regardless of route chloramphenicol administration. There were similar changes in chloramphenicol kinetic parameters in culture-negative patients. Antipyrine Cl(p) and liver blood flow correlated weakly with chloramphenicol Cl(p) in culture-positive patients (P < 0.1) and were higher in convalescence; no such associations were seen for iothalamate Cl(p). These data indicate that i.v. chloramphenicol produces peak plasma concentrations which are on average twice those after i.m. injection of the same dose, due principally to a smaller V(d)ss. Cl(p) is uninfluenced by route of administration and is determined more by hepatic metabolism than renal excretion. Intramuscular treatment may result in sub-therapeutic chloramphenicol concentrations initially, but continued regular i.v. dosing is more likely to produce levels at which bone marrow toxicity occurs.

Adolescent↗