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Biomedical subjects

J Taylor

Publications and source records attributed to J Taylor.

At least 37 records · Page 2Linked to original sources

Blinkered objections to bioethics: a response to Benatar.

In a recent commentary, S R Benatar criticised the debates over organ donation and kidney selling for being located within a "narrow and inadequate framework". Benatar levels four charges against those who engage in the current organs debate: that they myopically focus on saving lives; that they accept the dominance of market orientated approaches to health care; that they reify individualism, and that they engage in limited moral arguments. Given the importance of the organs debate it is imperative that the misunderstandings of it on which Benatar's criticisms are based are dispelled. Accordingly, I will consider and reject each of his objections in turn.

Bioethics↗

Trace element concentrations in patients on home enteral feeding: two cases of severe copper deficiency.

BACKGROUND: Enteral feeding is the fastest growing area of artificial nutrition, with the annual rate of growth being estimated at 20-25% a year. Previous studies have demonstrated trace element deficiencies in patients on long-term home enteral nutrition (HEN). METHODS: The trace elements zinc, selenium, copper and manganese were measured in blood samples from 37 patients on HEN using atomic absorption spectroscopy. RESULTS: Plasma zinc concentrations (range 7.4-14.4 micromol/L) were below the reference range (12.6-22.0 micromol/L) in 30 patients, plasma selenium concentrations (range 0.73-1.76 micromol/L) were below the reference range (0.8-2.0 micromol/L) in only one patient. Whole blood manganese (range 74-309 nmol/L) and plasma manganese (range 13-51 nmol/L) were above both respective reference ranges (73-210 nmol/L and 9-24 nmol/L) in four patients. Two patients showed severely low plasma copper concentrations of 2.4 micromol/L and 2.5 micromol/L, and responded to treatment with extra copper supplementation. CONCLUSION: Although enteral feeds contain adequate concentrations of trace elements, problems with bioavailability may occur and patients receiving long-term enteral feeding should be monitored with regard to plasma trace element concentrations.

Adult↗

Efficacy of chimeric molecules directed towards multiple somatostatin and dopamine receptors on inhibition of GH and prolactin secretion from GH-secreting pituitary adenomas classified as partially responsive to somatostatin analog therapy.

OBJECTIVE: This study compared the potency of a somatostatin receptor (sstr)2-sstr5 analog, BIM-23244, of an sstr2-dopamine D2 receptor (sstr2-DAD2) molecule, BIM-23A387 and of new somatostatin-dopamine chimeric molecules with differing, enhanced affinities for sstr2, sstr5 and DAD2, BIM-23A758, BIM-23A760 and BIM-23A761, to suppress GH and prolactin (PRL) from 18 human GH adenomas that are partially responsive to octreotide or lanreotide. MATERIALS AND METHODS: The sstr2, sstr5 and DAD2 mRNA levels were determined by RT-PCR. The effect of drugs was tested in cell cultures at various concentrations. RESULTS: In all tumors, the sstr2, sstr5 and DAD2 mRNA levels were coexpressed (mean levels+/-s.e.m. 0.4+/-0.1, 5.3+/-1.9 and 2.0+/-0.4 copy/copy beta-glucuronidase). In 13 tumors, the maximal suppression of GH secretion produced by BIM-23A387 (30+/-3%) and BIM-23244 (28+/-3%) was greater than that produced by octreotide (23+/-3%). In six out of 13 tumors, BIM-23A758, BIM-23A760 and BIM- 23A761 produced greater maximal suppression of GH secretion than octreotide (33+/-5, 38+/-2 and 41+/-2 vs 24+/-2%). Their EC(50) values were 10, 2 and 4 pmol/l. BIM-23A761 was more effective than BIM-23A387 in GH suppression (41+/-2 vs 32+/-4%). The new chimeric molecules produced maximal PRL suppression greater than octreotide (62+/-8 to 74+/-5 vs 46+/-11%). CONCLUSIONS: Novel dopamine-somatostatin chimeric molecules with differing, enhanced activity at sstr2, sstr5 and DAD2, consistently produced significatly greater suppression of GH and PRL than either octreotide or single-receptor-interacting ligands in tumors from patients classified as only partially responsive to octreotide therapy. The higher efficacy of the chimeric compounds was, at least partially, linked to their high affinity for sstr2 (IC50 1-10 pmol/l). The other mechanisms by which such molecules produce an enhanced inhibition of GH remain to be elucidated.

Acromegaly↗

The oral contraceptive pill effectively permits cycle batching for an intermittent in vitro fertilization programme in Trinidad and Tobago.

Assisted reproductive technology (ART) in small island states like Trinidad and Tobago is usually provided in batches so as to minimize the cost of providing the service. As a result, patients 'cycles have to be synchronized in order to coincide with the arrival of a visiting embryologist. This is a retrospective study which evaluates the experience of pre-treatment with an oral contraceptive pill (OCP) as a means of batching cycles for an intermittent ART programme. Seventy-four in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles in which OCP usage was employed (Group A), were compared with 121 cycles which did not require pharmaceutical manipulation (Group B). In both groups more than 50% of women were older than 36-years. Two cycles were cancelled in Group A and seven in Group B, because of poor ovarian response. Although the pregnancy rate per treatment cycle was higher in Group A than in Group B (26.3% vs 17.3%), this difference was not significant. More spontaneous miscarriages occurred in the non-OCP women and ovarian cyst formation was more common in these women. The authors experience indicates that the OCP is a simple, cheap and efficient means of batching patients for an intermittent ART programme and can be utilized in other small ART centres.

Adult↗

Impact of RO-desalted water on distribution water qualities.

A large-scale pilot distribution study was conducted to investigate the impacts of blending different source waters on distribution water qualities, with an emphasis on metal release (i.e. corrosion). The principal source waters investigated were conventionally treated ground water (G1), surface water processed by enhanced treatment (S1), and desalted seawater by reverse osmosis membranes (RO). Due to the nature of raw water quality and associated treatment processes, G1 water had high alkalinity, while S1 and RO sources were characterized as high sulfate and high chloride waters, respectively. The blending ratio of different treated waters determined the quality of finished waters. Iron release from aged cast iron pipes increased significantly when exposed to RO and S1 waters: that is, the greater iron release was experienced with alkalinity reduced below the background of G1 water. Copper release to drinking water, however, increased with increasing alkalinity and decreasing pH. Lead release, on the other hand, increased with increasing chloride and decreasing sulfate. The effect of pH and alkalinity on lead release was not clearly observed from pilot blending study. The flat and compact corrosion scales observed for lead surface exposed to S1 water may be attributable to lead concentration less than that of RO water blends.

Calcium Carbonate↗

BIM-23A760, a chimeric molecule directed towards somatostatin and dopamine receptors, vs universal somatostatin receptors ligands in GH-secreting pituitary adenomas partial responders to octreotide.

We report the comparative efficacy of a somatostatin receptor 1 and 5 subtypes (SSTR2 and SSTR5), and dopamine D2 (DAD2) compound, BIM-23A760, in suppressing GH secretion, in cell culture from human GH-secreting tumors, from patients partially responsive to long-term treatments with octreotide or lanreotide. In 18 tumors tested, the SSTR2, SSTR5, and DAD2 mRNAs were coexpressed. The SSTR2-selective analog, BIM-23197, the SSTR5-selective analog, BIM-23268, and the dopamine (DA) analog, BIM-53097, produced a mean maximal suppression of GH secretion (24 +/- 3, 20 +/- 3, and 20 +/- 3%, respectively) that was similar to that obtained with octreotide (23 +/- 3%). Nevertheless, based on individual responses, 60% of the tumors were mostly sensitive to the SSTR2 analog while 19 and 21% of the tumors were mainly responsive to the SSTR5 analog and to the DA analog, respectively. Among a series of new chimeric compounds that bind the SSTR2, SSTR5, and DAD2 receptors with variable affinities, BIM-23A760 produced greater maximal suppression of GH secretion than octreotide (38 +/- 2 vs 24 +/- 2%; p<0.03). The EC50 for BIM-23A760 was 2 pmol/l. In the presence of sulpride, the dose response inhibition of GH secretion by the trihybrid molecule, BIM-23A760, was partially reversed. The trihybrid produced also a maximal suppression of PRL greater than octreotide (74 +/- 5 vs 46 +/- 11%). When SSTRs pan inhibitors such as BIM-23A779 (binding affinity for SSTR1, SSTR2, SSTR3, SSTR5, respectively: 2.5, 0.3, 0.6, 0.6 nmol/l) or SOM230 were tested for their suppressive effects on GH secretion, they were less potent than the previous dopastatin hybrid molecule. After a brief exposure to a SSTR2-selective analog, BIM-23197, or to a DA analog, BIM-53097, the maximal GH suppression was achieved during 12 h. Under exposure to BIM-23A760, in the same conditions, maximal suppression of GH secretion lasted for 24 h. Such a longer biological effect, yet not explained, probably participates in the higher efficacy of BIM-23A760. The higher efficacy of BIM-23A760 is, at least partially, linked to its high affinity for the SSTR2 receptor subtype (IC50: 3 pmol/l). As compared to the dopastatin compound, the lower efficacy of the universal somatostatin ligands in the inhibition of GH secretion of GH-secreting tumors argues for the use of drugs targeted, according to specific receptors expression and functionality which may vary among the various classes of tumors.

Acromegaly↗

Physiology: does gut hormone PYY3-36 decrease food intake in rodents?

Batterham et al. report that the gut peptide hormone PYY3-36 decreases food intake and body-weight gain in rodents, a discovery that has been heralded as potentially offering a new therapy for obesity. However, we have been unable to replicate their results. Although the reasons for this discrepancy remain undetermined, an effective anti-obesity drug ultimately must produce its effects across a range of situations. The fact that the findings of Batterham et al. cannot easily be replicated calls into question the potential value of an anti-obesity approach that is based on administration of PYY3-36.

Animals↗

Endovascular treatment of abdominal aortic aneurysm.

BACKGROUND: Endovascular repair of abdominal aortic aneurysm has become widely used. Supporters claim high success rates, few complications and a dramatically reduced hospital stay. However, endoleak, endotension and reports of endoprosthesis rupture are causes of concern. METHODS: A Medline search was undertaken to identify articles on endovascular repair of abdominal aortic aneurysm. Additional papers were identified by manual scanning of the references from key articles. RESULTS AND CONCLUSION: Endoleak is a potentially serious complication of the endovascular technique and occurs in a significant proportion of patients. It is still not possible to judge whether the presence of an endoleak alone signifies failure of treatment, and the long-term durability of prosthetic covered stents is unknown. However, endovascular repair does appear to confer a degree of protection from rupture although patients must be advised of the need for life-long imaging surveillance and, perhaps, further intervention.

Aortic Aneurysm, Abdominal↗

Multiple-electrode nerve cuffs for low-velocity and velocity-selective neural recording.

In the paper, a method using multiple-electrode nerve cuffs is presented that enables electroneurographic signals (ENG) to be recorded selectively by action potential velocity. The theory uses a one-dimensional model of the electrodes in the cuff. Using this model, the transfer function for a single tripole is derived, and it is shown that more than one tripole signal can be recorded from within a cuff. When many tripole signals are available and are temporally aligned by artificial delays and summed, there is a significant increase in the amplitude of the recorded action potential, depending on the cuff length and the action potential velocity, with the greatest gain occurring for low velocities. For example, a cuff was considered that was constrained by surgical considerations to 30 mm between the end electrodes. For action potentials with a velocity of 120 m s(-1), it was shown that, as the number of tripoles increased from one, the peak energy spectral density of the recorded output increased by a factor of about 1.6 with three tripoles, whereas, for 20 m s(-1), the increase was about 19, with ten tripoles. The time delays and summation act as a velocity-selective filter. With consideration of the energy spectral densities at frequencies where these are maximum (to give the best signal-to-noise ratio), the tuning curves are presented for these velocity-selective filters and show that useful velocity resolution is possible using this method. For a 30 mm cuff with nine tripoles, it is demonstrated that it is possible to resolve at least five distinct velocity bands in the range 20-120m s(-1).

Action Potentials↗

Experimental determination of compound action potential direction and propagation velocity from multi-electrode nerve cuffs.

Information extracted from whole-nerve electroneurograms, recorded using electrode cuffs, can provide signals to neuroprostheses. However, the amount of information that can be extracted from a single tripole is limited. This communication demonstrates how previously unavailable information about the direction of action potential propagation and velocity can be obtained using a multi-electrode cuff and that the arrangement acts as a velocity-selective filter. Results from in vitro experiments on frog nerves are presented.

Action Potentials↗

Paying attention to meaning.

Several paradigms show that responses to one event compromise responses to a second event for around 500 ms. Such effects are generally attributed to attentional capacity limitations associated with processing information in the first event. In a task in which targets could be distinguished only by their meaning, we varied the semantic relationship between distractors and targets following at different lags. Semantic relatedness alone produced a classic attentional blink. We conclude by discussing how attention theory might best accommodate these new effects.

Attention↗

HIV-associated morbidity, mortality and diagnostic testing opportunities among inpatients at a referral hospital in northern Tanzania.

Hospitalized patients with HIV infection are among the most likely to benefit from the expanding availability of anti-retroviral therapy in sub-Saharan Africa. Between 1990 and 2000, 3667 people known to be HIV-infected were admitted to Kilimanjaro Christian Medical Centre (KCMC) in Moshi, northen Tanzania. The level of inpatient mortality among these patients varied from 15%-21%, and the proportion of the HIV-infected patients admitted who were female increased significantly, from 45% at the start of the study period to 52% at the end (P <0.001). When the medical records for 1683 of the HIV-infected patients who had been admitted between 1996 and 2001 were reviewed, the most prevalent diagnoses on admission were found to be pulmonary tuberculosis (21%), malaria (14%) and gastro-enteritis/diarrhoea (12%) among the adults, and non-tubercular pulmonary infection (21%), pulmonary tuberculosis (19%) and gastro-enteritis/diarrhoea (12%) among the children. The crude odds ratios (OR) for inpatient death were greatest for adults presenting with meningitis [OR=3.7; 95% confidence interval (CI)=2.1-6.7], septicaemia (OR=2.9; CI=1.2-7.3) or renal disease (OR=2.6; CI=1.2-5.7), and mortality was higher for men than for women (OR=1.4; CI=1.1-1.8). A single-day, point-prevalence survey in September 2001, among the KCMC's inpatients, identified HIV infection in 21% of those surveyed, many (44%) of the patients found positive being previously unaware of their infection. HIV infection remains a major cause of hospitalization and mortality in Moshi. A policy of routine testing would increase the number of HIV infections detected, allowing improvements in case management and in the prevention of infection.

Adolescent↗

The 6-min walk distance: change over time and value as a predictor of survival in severe COPD.

The 6-min walk distance (6MWD) is used to evaluate the functional capacity of patients with chronic obstructive pulmonary disease (COPD). The change in 6MWD over time and its correlation with changes in spirometry and survival are unclear. Patients (n=198) with severe COPD and 41 age-matched controls were followed for 2 yrs, and anthropometrics, spirometry, 6MWD and comorbidities were measured. The 6MWD decreased in the COPD group from 238 +/- 107 m to 218 +/- 112 m (-26 +/- 37 m x yr(-1)), and increased in the control group from 532 +/- 82 m to 549 +/- 86 m (12 +/- 25 m x yr(-1)). In both groups, there was a poor correlation with changes in forced expiratory volume in one second (FEV1). Nonsurvivors in the COPD group (42%) had a more pronounced change in the 6MWD (-40 versus -22 m x yr(-1)) but a similar change in FEV1 (118 versus 102 mL x yr(-1)). The 6MWD independently predicted survival, after accounting for age, body mass index, FEV1 and comorbidities. In severe chronic obstructive pulmonary disease, the 6-min walk distance predicts mortality better than other traditional markers of disease severity. Its measurement is useful in the comprehensive evaluation of patients with severe disease.

Anthropometry↗

Multislice CT in imaging of trauma of the spine, pelvis and complex foot injuries.

Multislice CT (MSCT) has greatly enhanced the performance of CT scanners and has vastly improved imaging of musculoskeletal trauma. Fast, high resolution scanning is now possible. In our institution, MSCT is an essential part of the imaging of the traumatized patient. The advantages of volume imaging, such as multiplanar reconstructions (MPRs) with near isotropic viewing, three-dimensional imaging and thick slice (wedge) MPRs (mimicking conventional radiographs), enable more accurate assessment of complex anatomical areas such as the spine, pelvis and foot. We discuss the general principles of scanning for musculoskeletal trauma and describe our experience of MSCT of the traumatized spine, pelvis and foot.

Clinical Protocols↗

Clostridium difficile: a questionnaire survey of laboratory practice in England, Wales, and Northern Ireland.

Since January 2004, the incidence of Clostridium difficile associated disease (CDAD) has been monitored by a systematic, national, laboratory surveillance system. This system incorporates the recommendations of a body of experts, the National Clostridium difficile Standards Group, which was convened in 2002 to advise the Department of Health (DoH). The recommendations of the group were informed by a questionnaire survey of current practice, and the results of that survey have been used to assess the implications of the recommendations on laboratory practice. Large variability was found as to the specimens selected, tested, and reported on for C. difficile. Standardisation of the diagnosis and reporting of CDAD is desirable and necessary to increase understanding of its epidemiology.

Clinical Laboratory Techniques↗

Alterations in skeletal muscle structure are minimized with steroid withdrawal after renal transplantation.

BACKGROUND: Limitations in exercise capacity in kidney transplant recipients are thought to result in part from changes in muscle structure and function associated with immunosuppression therapy. METHODS: We compared the percent distribution of skeletal muscle fiber types, cross-sectional areas, and ultrastructural morphologies in kidney transplant recipients treated with standard prednisone maintenance therapy (n=21) to those undergoing rapid withdrawal of prednisone using Simulect (interleukin 2 receptor inhibitor) (n=13). Skeletal muscle biopsy specimens from the vastus lateralis were analyzed at 3 and 12 months after transplantation and compared with sedentary controls (n=15). RESULTS: Compared with the control group, the group receiving prednisone maintenance therapy had a significantly lower percentage of type I fibers and a higher percentage of type IIB/x fibers, evident at 3 and 12 months. Fiber type distribution in patients withdrawn from prednisone did not differ from controls. In patients withdrawn from prednisone, the cross-sectional areas of type I and IIA fibers were lower and the area of type IIB/x fibers was higher compared with controls. Likewise, ultrastructural studies revealed reduced volume densities of myofibrils and higher densities of interfibrillar and subsarcolemmal mitochondria. At 12 months there were no ultrastructural differences between the patients withdrawn from prednisone and controls. CONCLUSIONS: We conclude that prednisone maintenance therapy contributes to the lower exercise capacity by altering the ratio of type I to type IIB/x fibers and by reducing myofilament density. The increase in mitochondria in patients receiving prednisone may reflect a switch from carbohydrate to lipid metabolism resulting from the glucocorticoid therapy.

Adult↗

Long-term outcomes of brachiobasilic transposition fistula for haemodialysis.

OBJECTIVES: The transposed basilic vein to brachial artery arteriovenous fistula provides secondary vascular access for haemodialysis. The long-term results of such fistula are assessed in this retrospective series. MATERIAL AND METHODS: Over a 5-year period 75 brachiobasilic transposition fistulae were performed in 74 patients. There was a median follow up of 14 months. RESULTS: Primary patency was achieved in 69 (92%) of the fistulae, and secondary patency in 74 (99%) of the fistulae. Successful interventions included angioplasties in four, and saphenous vein interposition in one, whilst three patients had failed thrombectomies. Dialysis was performed using 69 (92%) of the fistulae while 6 (8%) were never used. Of the 75 fistulae 47 (63%) were patent at follow up. Cumulative secondary patency was 66% at 1 year, 52% at 2 years, and 43% at 3 years. Complications developed in 41 (55%), and included thrombosis, infection, stenosis, arm oedema, bleeding, steal syndrome and microaneurysm formation. CONCLUSIONS: Brachiobasilic transposition fistulae have good long-term patency rates. The complication rate, although high, is lower than that reported for PTFE grafts. Brachiobasilic fistulae should be used in preference to PTFE grafts for secondary access.

Adolescent↗

Should we biopsy kidneys of patients post-liver transplant?

Thirty days after orthotropic liver transplantation, a 52-year-old Hispanic male developed full-blown nephrotic syndrome. Although the patient was posttransplantation, he underwent a kidney biopsy under real-time ultrasound guidance. The pathological specimen revealed membranous nephropathy. A change in the immunosuppressive regimen resulted in a rapid decrease in urinary protein excretion, leading to resolution of the nephrotic syndrome. We report this case to illustrate the precautions that need to be taken when liver transplant patients require a kidney biopsy.

Biopsy↗