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Biomedical subjects

S Morris

Publications and source records attributed to S Morris.

At least 109 records · Page 6Linked to original sources

Characterization of fatty acid clearance in premature neonates during intralipid infusion.

This study reports the clearance of plasma triglyceride and phospholipid fatty acids during Intralipid 20% infusion (Pharmacia, Sweden) in nine ventilated preterm infants receiving parenteral nutrition. Blood samples were taken during lipid infusion and over a subsequent period of 36 h of fat-free parenteral nutrition. Plasma triglyceride fatty acids showed a uniform and rapid decline after lipid was stopped from the peak values recorded during infusion. In contrast, plasma phospholipid fatty acids showed a variable decline during fat-free nutrition. This variability appeared to be the result of a differing contribution of infused egg yolk phospholipid fatty acids to the measured plasma values, and to changing fatty acid composition of endogenous phospholipid in response to fat free nutrition. Red cell phospholipid fatty acid composition was stable over the 36-h clearance study period. These results indicate the complexity of interpretation of plasma fatty acids during lipid infusion. We conclude that red cell phospholipid fatty acids provide the only stable measure of tissue fatty acid composition in parenterally fed preterm infants.

Fat Emulsions, Intravenous↗

Strategies for migration in the terrestrial christmas island red crab gecarcoidea natalis: intermittent versus continuous locomotion

The terrestrial red crab Gecarcoidea natalis undertakes an annual breeding migration and must sustain locomotion for prolonged periods. The migrating crabs must travel a specific distance in a fixed time and can either walk at a constant speed or walk faster for short periods and then pause to feed or rest. To simulate the potential differences between continuous and intermittent locomotion during the migration, red crabs were sampled after walking at a voluntary speed for 5 or 20 min without pausing or after 20 min of enforced walking intermittently at approximately twice that speed. The respiratory and metabolic status of the crabs was investigated during the different exercise regimes to assess which strategy might be more advantageous during the migration. The gills and lungs appeared to function similarly in gas exchange, and the PO2 in the haemolymph was 8.2 kPa which fully saturated the haemocyanin with O2. The uptake of O2 by red crabs was diffusion-limited and the diffusion coefficient (Ldiff) varied from 0.53 in resting crabs to 0. 8 post-exercise. Post-exercise, red crabs experienced a mixed respiratory/metabolic acidosis which was greatest (0.2 pH units) in crabs walking intermittently, i.e. at a higher speed. Haemolymph l-lactate concentrations peaked at 5 mmol l-1 immediately post-exercise in the intermittent exercise group, whereas after 20 min of continuous exercise haemolymph l-lactate continued to increase, reaching a maximum of 2.5 mmol l-1 at 1 h post-exercise. l-Lactate recovered slowly to basal levels within 5 h. The maximum rate of l-lactate clearance from the haemolymph was only 1.75 mmol l-1 h-1, and short pauses in exercise were insufficient for substantial l-lactate reoxidation. Exercise regimes in the laboratory were within the locomotor speeds determined for migrating red crabs, which overall have a mean walking speed close to their aerobic limit but periodically pause and also exceed this limit by three- to fourfold.

Journal Article↗

The functioning of the haemocyanin of the terrestrial christmas island red crab gecarcoidea natalis and roles for organic modulators

Gecarcoidea natalis is a land crab that migrates annually several kilometres to breed. The O2-binding properties of haemocyanin in G. natalis were investigated in vitro to test the idea that the O2-binding properties of the haemocyanin of land crabs are not dependent on circulating modulators and to provide a model of haemocyanin functioning during exercise. The affinity of the haemocyanin for O2 decreased with increasing temperature (change in the heat of oxygenation; capdelta H=-59 kJ mol-1). The haemocyanin of G. natalis apparently differs from that of other terrestrial crabs in showing haemocyanin O2 modulation by both organic and inorganic molecules. Haemocyanin O2-affinity was not affected by Mg2+ but was sensitive to changes in Ca2+ concentration ( capdelta logP50/ capdelta log[Ca]=-0.61, where P50 is the partial pressure of O2 required for half-maximal O2 binding). The Bohr factor was modest ( &phgr; =-0.26+/-0.03, N=4, in whole haemolymph at 25 degreesC) and there was no specific effect of CO2 on the O2-binding properties of the haemocyanin. An increase in urate concentration increased haemocyanin O2-affinity, but the effect was linear ( capdelta logP50/ capdelta [urate]=-0.06) and not logarithmic as is the case in other species. The effect of l-lactate on the haemocyanin O2-affinity in G. natalis was unique among the crustaceans, because an increase in l-lactate concentration decreased the haemocyanin O2-affinity. The effect of l-lactate on haemocyanin O2-affinity ( capdelta logP50/ capdelta log[lactate]) was time-dependent and decreased from a maximum of 0.044 on day 1 to 0.001 after 4 days of storage at 4 degreesC. The presence of an unknown dialysable and unstable factor in the haemolymph is postulated to explain the time-dependent effect of l-lactate on haemocyanin O2-binding properties. Model oxygen equilibrium curves constructed for in vivo conditions showed that the reverse effect of l-lactate was advantageous by decreasing the O2-affinity of the haemocyanin beyond that predicted by the Bohr shift alone and assisted in O2 off-loading at the tissues. This effect of lactate can only provide an advantage if the gas-exchange organs maintain arterial O2 loading and thus is dependent on lung function in land crabs and must have occurred coincident with the evolution of these other features.

Journal Article↗

Salt and water relations, and nitrogen excretion, in the amphibious african freshwater crab potamonautes warreni in water and in air

Mechanisms of salt and water conservation, and nitrogen excretion, were investigated in the freshwater amphibious crab Potamonautes warreni from the High Veld of South Africa. Adaptations to fresh water were assessed as pre-adaptations to air-breathing, and nitrogen excretion was examined as a potential constraint to terrestrial excursions. P. warreni was able to regulate water and salt loss in water up to 40 % sea water, but not in 80 % sea water. The water permeability of P. warreni was low and, since 97 % of the haemolymph filtrate was reabsorbed in the antennal organ, urinary water loss was minimal (0.7 microl g-1 h-1). The minimum equilibrium [Na] of P. warreni was low (0.116 mmol l-1), as were the rates of both Na loss (0.22 micromol g-1 h-1) and Ca loss (0.29 micromol g-1 h-1). The low loss rates were due to urinary salt conservation of approximately 90 % or better and to low permeability (K'Na=0.0025; K'Ca=0.0521), and were compensated for by a high-affinity uptake mechanism (Jmax=0.76 micromol g-1 h-1 and Km=0.18 mmol l-1). Acclimating P. warreni to low Na concentrations increased maximum net Na uptake rate to 1.77 micromol g-1 h-1. Nitrogen excretion in P. warreni was almost 100 % ammoniotelic, and there was no accumulation of haemolymph or urinary ammonia or urea when in air. P. warreni was unable to excrete ammonia to air, but in water the rate of excretion was nearly 70 micromol kg-1 h-1. Crabs in amphibious conditions showed pulses of elevated NH3 excretion (350 micromol kg-1 h-1) when subsequently submerged, while for crabs breathing air for 3 days this pulse reached 4.9 mmol kg-1 h-1. Air-breathing P. warreni with artificially irrigated branchial chambers excreted double the amount of NH3 via the gills compared with crabs from amphibious conditions. Water and salt conservation form useful pre-adaptations to terrestrial forays. While the relatively low water loss extends the duration of emersion, P. warreni is required to return briefly to water to excrete stored nitrogenous waste. The nature of the store remains to be determined.

Journal Article↗

Combination therapy for HIV: the effect on inpatient activity, morbidity and mortality of a cohort of patients.

We set out to quantify the changes in HIV-related morbidity and mortality associated with the clinical use of antiretroviral therapy via prospectively collected patient-related events (admissions, bed days, deaths, WHO stage 3 and 4 events and drug costs) on all HIV patients known to the Regional Infectious Disease Unit (RIDU) from 1 January 1987 to 31 December 1996. The introduction of zidovudine monotherapy in 1987 for those with AIDS was associated with a subsequent decline of inpatient activity for 2 years: in 1989 there was a 23% reduction in bed days but only a 6% reduction in admissions. A further dramatic decline of patient-related events in those with AIDS was noted during 1996 following the introduction of combination therapy, a 39% reduction in admissions, 44% reduction in bed days, 54% reduction in stage 4 events, 33% reduction in WHO stage 3 events and 40% reduction in the death rate. Reductions were also observed for patients without AIDS including a 42% reduction in the rate of patients developing AIDS. Similar reductions were noted when the patients were classified by immunological instead of clinical status although data for 1997 suggest an increase in patient-related activity for those with CD4 counts >200 cells/microl possibly as a result of low levels of anti-HIV therapy. The introduction of combination therapy for HIV has to date led to a minimum saving of one inpatient bed per 100 patient years which helped defray the cost of combination therapy. Although we cannot imply causality from an observational study, dramatic reductions in patient-related activity were associated with the introduction of combination therapy into clinical practice. The ultimate extent and duration of this effect cannot as yet be predicted and caution is required since similar reductions were noted with zidovudine therapy which were unfortunately time limited.

Anti-HIV Agents↗

Predictors of co-incidental CIN II/III amongst a cohort of women with CIN I detected by a screening Pap test.

Approximately 20-40% of lesions interpreted by a screening Pap test as CIN I and subsequently examined by colposcopy include a co-incidental CIN II/III. Since the HPV profiles of CIN I and CIN II/III differ, HPV typing may predict these co-incidental higher grade lesions. Based on both the colposcopic impression and repeat Pap test, 537 women referred for examination of CIN I as classified by a screening Pap test were triaged into group A (</= CIN I) or group B (>/= CIN II). Clinical, demographic, reproductive, and risk factor data was collected by questionnaire and HPV typing of cervical scrapes was done by PCR. Group A included 342 (63.7%) women and group B 195 (36.3%). Group B women more frequently were current cigarette smokers (p<0.001) and had a high school or lesser level of education (p=0.04). HPV positivity amongst younger group B women (</= 21 years) and a history of current/occasional cigarette smoking in those 22 years and older were significant predictors of triaged, co-incidental CIN II/III (p<0.001). This age restriction will limit the adoption of HPV testing as an universal, adjunctive test for the identification of CIN II/III amongst CIN I lesions detected by a screening Pap test. A greater health advantage may be gained by increasing women's awareness of the risks, including that of cervical cancer associated with cigarette smoking.

Adult↗

Use of toenail fluoride levels as an indicator for the risk of hip and forearm fractures in women.

The relation between fluoride intake and risk of osteoporotic fractures remains unclear. The lack of individual measures of long-term fluoride intake has limited epidemiologic studies. We used toenail fluoride in this study as a measure of long-term intake to evaluate the relation between fluoride intake and subsequent risk of hip and distal forearm fractures. Between 1982 and 1984, we collected toenail clippings from 62,641 women in the Nurses' Health Study who were free from cancer, heart disease, stroke, and previous hip or forearm fracture. We identified fracture cases (53 proximal femur and 188 distal forearm) through subsequent biennial mailed questionnaires and matched controls to cases on year of birth. The odds ratio of hip fracture among women in the highest quartile of toenail fluoride [ > 5.50 parts per million (ppm)], compared with those in the lowest quartile (> 2.00 ppm), was 0.8 (95% confidence interval = 0.2-4.0), with adjustment for menopausal status, postmenopausal hormone use, caffeine intake, and alcohol consumption. The corresponding adjusted odds ratio for forearm fracture was 1.6 (95% confidence interval = 0.8-3.1). Further adjustment for body mass index, smoking status, and calcium and vitamin D intake did not alter these results.

Adult↗

The natural history of CIN I lesions.

The published literature indicates 11% of CIN I lesions on average progress to a higher grade dysplasia and the remainder either regress or persist. Reliable markers of disease outcome are yet to be identified. A longitudinal study of 342 women referred for colposcopic examination of a CIN I detected by a screening Pap test, and classified by the colposcopic impression and Pap test at that exam as </= CIN 1 was designed to identify predictors of disease outcome. The cohort was comprised of 220 women who satisfactorily completed the study and whose disease was neither biopsied or treated at the initial examination. All had HPV DNA testing by PCR, and were followed with interval colposcopic examinations and repeat Pap tests for a limited time period. The initial HPV DNA status and a number of measured clinico-pathological and risk factor variables were analyzed to identify outcome predictors. All underwent a biopsy either at the conclusion of the study or because their disease was considered to have progressed during the follow up period. Biopsy confirmed progression to CIN II/III occurred in 41 (18.6%), persistence of CIN I/Condyloma in 41 (18.6%), and regression to <CIN I/Condyloma in 138 (62.7%). HPV DNA positivity and current, oral contraceptive use were the only independent predictors of progression when age at diagnosis, the number of follow up visits, and time to progression were controlled. Predictors of persistent and regressed disease were not identified. The study highlights a clinical role for HPV testing in the colposcopic management of CIN I lesions. Oral contraceptives may promote progression by regulating the oncogenic sequences of the HPV.

Adolescent↗

Physical, psychiatric and social characteristics of the temporomandibular disorder pain dysfunction syndrome: the relationship of mental disorders to presentation.

OBJECTIVE: To investigate the physical and psychosocial characteristics and to identify the prevalence of mental disorders in pain dysfunction syndrome (PDS). DESIGN AND SETTING: New referrals to temporomandibular disorder clinics at Manchester Dental Hospital and diagnosed with PDS. METHODS: Patients were assessed with a range of socio-demographic, dental and psychosocial measures including a psychiatric interview. Patients with PDS and a mental disorder were compared with those without a mental disorder. RESULTS: 97 patients were included; 32 (33%) had a mental disorder. There were no significant differences between those with and those without a mental disorder on any of the objective dental measures. Those with a mental disorder complained of more pain associated with PDS. They reported more anxiety and depression and also more physical symptoms unrelated to the PDS for which they had sought help and received more treatments. CONCLUSIONS: Psychosocial factors contribute to the presentation and possibly causation of PDS in the third of patients seen in a hospital setting who have a mental disorder. This factors should be considered when managing patients with PDS.

Adolescent↗

Cytomegalovirus gB genotype distribution differs in human immunodeficiency virus-infected patients and immunocompromised allograft recipients.

Cytomegalovirus isolates can be grouped into 4 gB and 2 gH genotypes. gB genotypes were studied in patients infected with human immunodeficiency virus (HIV) and in allograft transplantation recipients. In allograft recipients, the distribution of gB 1, -2, -3, and -4 in leukocytes and urine, respectively, was 36%, 21%, 43%, and 0% and 39%, 30%, 17%, and 13%. However, in leukocytes of HIV-infected patients with <100/microL CD4 cells, gB1 was found significantly less often than in allograft recipients (11% vs. 36%) but gB2 was more frequent (56% vs. 21%; P < .05). The decreased incidence of gBl and increased incidence of gB2 compared with allograft recipients was also seen in urine of HIV-infected patients and reflected the distribution seen in leukocytes. gB4 was found significantly more often (P < .05) in semen than in leukocytes of HIV-infected patients with < 100/microL CD4 cells. gB1-4 genotypes were similar in patients with < 100/microL CD4 cells with or without retinitis.

AIDS-Related Opportunistic Infections↗

Damage to the laryngeal mask by residual fluid in the cuff.

It has been suggested that, in some situations, the cuff of the laryngeal mask should be filled with fluid. We speculated that this practice might damage the device during sterilisation in an autoclave. We studied whether injection of a small volume of water into the cuff of the laryngeal mask and subsequent sterilisation affected the integrity of the cuff. First, a pressure-volume relationship for each of 20 new masks was obtained by inflating the cuff with increasing volumes of air (5-45 ml). The masks were then randomly allocated into four groups (W0, W0.25, W0.5 or W1.0), 0, 0.25, 0.5 or 1.0 ml of water was injected into the cuff and the mask was then sterilised in an autoclave. After sterilisation, the shape of the cuff was examined and pressure-volume relationships were obtained again. The baseline intracuff pressures were similar in the four groups. After sterilisation, the pressure was significantly lower in groups W0.25, W0.5 and W1.0 than in group W0 (p < 0.05). Two masks in group W1.0 lost their integrity, resulting in herniation of and rupture of the cuff. We conclude that the cuff of the laryngeal mask should not be inflated with fluid unless the device is discarded afterwards.

Equipment Failure↗

Multiple biological roles associated with the Rous sarcoma virus 5' untranslated RNA U5-IR stem and loop.

The 5' untranslated region of Rous sarcoma virus (RSV) RNA is a highly ordered structure involved in multiple processes in the viral replication cycle. One of these structures, referred to as the U5-IR stem, is located immediately upstream of the 5' end of the primer binding site. Disruption of its base pairing results in a decrease in initiation of reverse transcription (D. Cobrinik, A. Aiyar, Z. Ge, M. Katzman, H. Huang, and J. Leis, J. Virol. 65:3864-3872, 1991). In the present study, the length of the U5-IR stem structure has been extended by insertions of different sequences which decrease the efficiency of reverse transcription, in vivo and in vitro. Reverse transcription is rescued partially by placing single-stranded bulges into the middle of the extended duplexes. Nucleotide substitutions or insertions into the loop region of the U5-IR stem also decrease the efficiency of reverse transcription, suggesting that these sequences may specifically interact with reverse transcriptase. Surprisingly, all of the extended stem mutations cause significant RNA packaging defects. In contrast, nucleotide insertions or base substitutions in the U5-IR loop do not affect RNA packaging. These data indicate that the reverse transcription initiation complex and RNA packaging apparatus are influenced by the same region of RSV RNA and that each process is differentially sensitive to changes in sequence and/or secondary structure.

Animals↗

Strategies for the management of hypercholesterolaemia: a systematic review of the cost-effectiveness literature.

OBJECTIVE: To review research addressing the management of cholesterol in the prevention of coronary heart disease in order to assess the cost-effectiveness of such interventions. METHODS: A systematic review of economic evaluations identified through searches of MEDLINE and the Social Sciences Citation Index revealed 38 studies addressing the cost-effectiveness of cholesterol management. They were distinguished according to screening approaches, dietary advice and drug treatment. Most studies were not associated directly with clinical trial results, but adopted economic modelling approaches. RESULTS: Whilst there is general agreement among the majority of analyses, studies of cholesterol management concerned with screening strategies were extremely sensitive to changes in their assumptions; so much so that only a limited emphasis may be placed on specific cost-effectiveness ratios and the conclusions drawn from them. All studies considered direct costs, though many were limited to drug costs. The cost-effectiveness of primary prevention by cholesterol-lowering drugs is highly variable, depending on age at initiation of treatment and cardiovascular risk profile. Pharmacological intervention is least cost-effective in the young and the elderly. The cost-effectiveness of cholesterol-reducing agents improves when they are targeted at those at high risk. HMG-CoA reductase inhibitors are generally more effective and more cost-effective at reducing cholesterol-related coronary events than other medications. CONCLUSION: The methods and economic data upon which these studies are based need to be improved if robust policy conclusions are to be formulated.

Anticholesteremic Agents↗

The cost of depression in the elderly. Effects of drug therapy.

Depression is a widespread and debilitating illness that affects an individual's ability to carry out their usual activities. It is therefore likely to represent a considerable economic and social burden to society. The prevalence of depression in the elderly has been estimated at around 10%, although it has been suggested that the level of undetected and untreated depression may be especially high in this group. The direct and indirect costs associated with depression in the elderly are therefore likely to be considerable. The application of economic analysis to drug therapy in the treatment of depression has so far been limited. There are no economic studies of the cost effectiveness of antidepressant drug therapy that concentrate exclusively on the treatment of the elderly. Available evidence across all groups suggests that selective serotonin reuptake inhibitors may be more cost effective than tricyclic antidepressants. This is primarily attributable to the lower incidence of adverse effects with the former. Whilst these results may be replicated in the elderly, there are specific characteristics of the elderly population which suggest that it may not be possible to generalise results. These include adverse effects, the costs of detection, the costs of noncompliance, and indirect costs and benefits. Therefore, further research and careful economic evaluation of the treatment of depression in the elderly is necessary to take account of these characteristics.

Aged↗

The HPV determinants of CIN I.

Correlates of HPV amongst a cohort of women with a CIN I detected by a screening Pap test were investigated. Co-incident CIN II/III lesions were identified and their influence on the HPV status and HPV determinants of screening detected CIN I was assessed. Based on both the colposcopic impression and repeat Pap test, 537 women referred for examination of a Pap test classified as CIN I were triaged into two groups. Group A lesions were assessed as </= CIN I; n = 342 (63.7%) and group B as >/= CIN II; n = 195 (36.3%). Clinical, demographic, reproductive, and risk factor for cervical cancer correlates were collected. HPV typing of cervical scrapes collected at the colposcopic examination was done by PCR amplification using seven sets of type specific and one set of consensus primers. HPV positivity was identified in 47% of all scrapes; types 16/18 (28%), 31/33/35 (10%), 6/11 (2%), and unknown (7%). The HPV status of the cohort and group A were very similar. Group B had a slightly higher rate of HPV positivity (52%) due to an increase in types 16/18. Statistically significant correlates of HPV prevalence or type were not identified either for the entire group or both triage groups, however in each group, HPV positive women tended to be younger and to have more sexual partners. Co-incident CIN II/III spuriously increased the HPV prevalence rate of CIN I detected by a screening Pap test. The HPV appears to be sexually transmitted both in low and high grade lesions and explains why the HPV determinants of the entire cohort were unaffected by the co-incident CIN II/III.

Adolescent↗