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Biomedical subjects

R Jones

Publications and source records attributed to R Jones.

At least 361 records · Page 20Linked to original sources

Feasibility and cost-effectiveness of outpatient autotransplants in multiple myeloma.

This report summarizes 2 years experience in performing 336 autotransplant procedures in 251 consecutive patients with multiple myeloma, using high-dose melphalan at 200 mg/m2 in the context of a tandem transplant program. A total of 91 patients received 118 transplants as outpatients while the remaining 160 patients received 218 transplants as inpatients. Outpatients were more often younger, with better stem cell products, normal serum albumin and beta-2-microglobulin levels as well as chemotherapy-sensitive disease compared to inpatients. There were no differences in hematopoietic recovery and non-hematologic toxicities between outpatient and inpatient transplant recipients. Post-transplant febrile neutropenia and most other post-transplant toxicities were managed successfully in an ambulatory setting. Although liberal criteria were developed for hospitalization of outpatients, including clinical parameters as well as patient desire and physician/nurse judgement, only 21% of outpatients required admission after transplantation. Median hospital stay for these outpatients was 9 days, while inpatients were hospitalized for a median of 15 days (P = 0.0001). After adjusting for differences in disease and host features, our study showed outpatient management resulted in significant financial savings due to lower pharmacy (42%), hospitalization (50%) and pathology/laboratory charges (36%). We conclude that outpatient transplants should facilitate access to myeloablative therapy, thereby improving complete remission rates and survival of myeloma patients.

Adult↗

An evaluation of near-patient testing for Helicobacter pylori in general practice.

INTRODUCTION: A knowledge of Helicobacter pylori status is likely to be important in the management of patients presenting in general practice with dyspepsia. Near-patient testing kits for the detection of the H. pylori antibodies in whole blood, which provide results very quickly, are now available. AIM: To determine the test characteristics of the Helisal Rapid Blood test in general practice and to describe the ways in which general practitioners incorporate the results of H. pylori testing into their management of patients with dyspepsia. SETTING: Nine general practices in the United Kingdom. PATIENTS: Consecutive patients presenting with dyspepsia in whom further investigation or referral was considered. METHODS: A whole blood fingerstick sample was tested for H. pylori antibodies using the Helisal Rapid Blood test and a venous sample was obtained for subsequent laboratory testing using Helisal Serum and Helico G (ELISA) methods. Results of the three tests were compared and analysed. Clinical data were recorded by the general practitioners. RESULTS: Full serological data were obtained on 123 patients, mean age 44.8 years. The sensitivity and specificity of the Helisal Rapid Blood test, compared with concordant results of the laboratory tests, were 83% and 78%, respectively. The prevalence of H. pylori-positive patients was 57%, with a positive predictive value of 83% and a negative predictive value of 78%. The results of the test had a significant impact on the clinical management of the patients in the study. COMMENT: The Helisal Rapid Blood test is a useful and convenient method of improving the clinical care of patients with dyspepsia in general practice.

Adolescent↗

Genetic variation segregating in natural populations of Tribolium castaneum affecting traits observed in hybrids with T. freemani.

We investigated patterns of within-species genetic variation for traits observed in hybrids (hybrid numbers, hybrid sex ratios, and hybrid male deformities) between two species of flour beetles, Tribolium castaneum and T. freemani. We found genetic variation segregating among four natural populations of T. castaneum as well as within these populations. For some hybrid traits, we observed as much variation among populations 750 km apart as between populations on different continents, suggesting genetic differentiation at a local scale. Within natural populations, the variation segregating among sires is greater than that found in an earlier study for an outbred laboratory population and comparable to that observed between inbred lines derived from the outbred stock by eight generations of brother-sister mating. When sires from T. castaneum are mated to conspecific and heterospecific females, we do not observe a significant correlation at the level of the family mean between the intraspecific and interspecific phenotypes, suggesting the independence of the hybrid traits from comparable traits within species. We discuss our findings in relation to the evolutionary genetics of speciation and the expression of epistatic genetic variance in interspecific crosses.

Animals↗

Cloning and sequence analysis of rat fertilin alpha and beta--developmental expression, processing and immunolocalization.

Fertilin alpha and beta are members of the MDC (metalloproteinase-like, disintegrin-like, cysteine-rich) protein family and are expressed on the sperm surface where they have been proposed to play a role in mammalian fertilization. Inhibition of sperm-oocyte binding and sperm-oocyte fusion make fertilin an attractive target for the development of an immunocontraceptive vaccine. Full-length cDNAs encoding alpha and beta fertilin subunits were isolated from a rat testis cDNA library and sequenced. Using reverse transcription-polymerase chain reaction (RT-PCR), the developmental expression of fertilin alpha and beta was determined in pre-pubertal and mature rat testes. Fertilin alpha mRNA was present at all stages of development, suggesting that it is not exclusively expressed in post-meiotic germ cells. In contrast, fertilin beta mRNA was first identified in day 19 testes, coincident with the presence of pachytene spermatocytes. Polyclonal antisera raised against a 28-residue peptide (corresponding to part of the disintegrin domain) and two recombinant fusion proteins identified a 90 kDa protein in testicular sperm extracts and a 60 kDa protein in caput and cauda epididymidal sperm extracts, the predicted sizes for rat fertilin beta precursor and mature protein respectively. Indirect immunofluorescence using the anti-peptide antisera stained the acrosomal cap of permeabilized testicular, caput and caudal spermatozoa and elongating spermatids in testicular sections.

ADAM Proteins↗

Comparison of the monocular occlusion and a direct method for objective measurement of fixation disparity.

PURPOSE: Previous studies have measured objective fixation disparity using a monocular occlusion method, by which the monocular components of misalignment are revealed by measuring the shift in the position of the fixating eye after occlusion of the other eye. METHODS: We assessed the use of the monocular occlusion method by comparing it to direct measurements of binocular vergence. RESULTS: The direct method required precise calibration, but was found to be reliable. Several problems were discovered with the monocular occlusion method: (1) when using a central fusion stimulus, fixation was difficult to control accurately enough to measure the small monocular shifts in eye position expected at lower vergence demands; (2) with a peripheral fusion target, objective fixation disparity could not be measured directly; and (3) upon occlusion, a variable saccade occurred in the fixating eye. CONCLUSION: Objective measurement of fixation disparity with the direct method is quicker and more reliable than with the monocular occlusion method.

Adult↗

Improving the detection rate of early gastric cancer requires more than open access gastroscopy: a five year study.

BACKGROUND/AIMS: To explore the reasons why patients with gastric cancer continue to present with advanced disease despite open access gastroscopy. PATIENTS: All patients diagnosed with gastric cancer between 1 August 1989 and 31 July 1994. METHODS: A retrospective study of the presentation of gastric cancer in South Tees; patients were diagnosed at open access gastroscopy or referred through conventional channels. Primary care records of 81 patients dying between 1991 and 1995 were analysed for previous symptoms, investigations, and antisecretory drug therapy. Findings were compared with 200 age and sex matched controls. RESULTS: The overall incidence of earlier stage gastric cancer remains low at 13%. Diagnostic delay occurs in both primary and secondary care due to a high incidence of previous dyspepsia and investigation. One in six patients had been previously investigated in the three years prior to diagnosis, the majority of whom were on antisecretory drugs. CONCLUSIONS: Early gastric cancer remains rare in South Tees health district. Advantages of open access gastroscopy appear to be compromised by delayed referral to hospital and failure of endoscopists to recognise the early disease; either they are unaware of its appearance or prior treatment with an H2 receptor antagonist masks the disease by allowing mucosal healing.

Aged↗

Childhood Lead Poisoning in Russia: A Site-specific Pediatric Blood Lead Evaluation.

Lead poisoning in children is an international concern. Health effects vary according to a child's blood lead level. Historically, the problem of lead poisoning in Russia had been defined by analysis of hair samples. In Saratov, Russia, during the spring of 1996, the authors conducted the first evaluation of blood lead levels among Russian children. The mean blood lead level of 579 samples analyzed at the Centers for Disease Control and Prevention was 7.7 µg/dL (range 3.0 to 35.7 µg/dL). The sensitivity of hair analysis in identifying blood lead levels above 10 µg/dL was 50%. Most of the environmental samples evaluated (including water, dust, paint, and soil) were within acceptable U.S. remediation standards. Almost one-fourth of the Russian children evaluated during this site-specific investigation had blood lead levels capable of causing adverse health effects in children. Hair analysis is not an adequate method for identifying these children. Additional investigations in other Russian cities are necessary in order to determine the extent of lead poisoning in Russia's children.

Journal Article↗

Acute and one-year outcome of a randomised controlled trial of brief cognitive therapy for major depressive disorder in primary care.

BACKGROUND: The consensus statement on the treatment of depression (Paykel & Priest, 1992) advocates the use of cognitive therapy techniques as an adjunct to medication. METHOD: This paper describes a randomised controlled trial of brief cognitive therapy (BCT) plus 'treatment as usual' versus treatment as usual in the management of 48 patients with major depressive disorder presenting in primary care. RESULTS: At the end of the acute phase, significantly more subjects (P < 0.05) met recovery criteria in the intervention group (n = 15) compared with the control group (n = 8). When initial neuroticism scores were controlled for, reductions in Beck Depression Inventory and Hamilton Rating Scale for Depression scores favoured the BCT group throughout the 12 months of follow-up. CONCLUSIONS: BCT may be beneficial, but given the time constraints, therapists need to be more rather than less skilled in cognitive therapy. This, plus methodological limitations, leads us to advise caution before applying this approach more widely in primary care.

Acute Disease↗

Lateral mobility of plasma membrane lipids in bull spermatozoa: heterogeneity between surface domains and rigidification following cell death.

Compartmentalization of surface membrane antigens into discrete regions or domains is a characteristic feature of differentiated cells. In mammalian spermatozoa at least 5 surface domains are known, implying the presence of barriers or boundaries within the plasma membrane. Using the technique of fluorescence recovery after photobleaching (FRAP) to measure diffusibility of fluorescent lipid analogues 1,1'-dihexadecyl-3,3,3'3'-tetramethylindocarbocyanine (DiIC[16]) and 5-(N-octa-decanoyl) aminofluorescein (ODAF), we have investigated lipid topology and dynamics in the plasma membrane of ejaculated bull spermatozoa. Contrary to reports in the literature, we have found that DiIC(16) stains only dead or damaged spermatozoa whereas ODAF intercalates into the plasma membrane of both live and dead cells, each type showing a distinctive staining pattern. FRAP analysis with ODAF revealed that diffusion coefficients on live spermatozoa are significantly faster on the acrosome and postacrosome (29.3x10(-9) cm2/second) than on the midpiece and principal piece (11.8x10(-9) cm2/second). Recovery (R) is >90% in all domains. ODAF diffusion also shows regionalized temperature-sensitivity with a 4-fold increase over the sperm head and a 1.8-fold increase on the tail between 20 degrees C and 37 degrees C. Remarkably, dead or permeabilized spermatozoa rapidly develop a large immobile phase (R<25%) over the whole plasma membrane. This rigidification is temperature insensitive and irreversible suggesting major changes in the physical state of membrane lipids. It is concluded that lipid diffusion in the plasma membrane of live bull spermatozoa is rapid and varies significantly between surface domains. Following permeabilization or cell death, however, a large immobile phase develops indicating substantial changes in membrane lipid disposition.

Animals↗

A search for sex-specific antigens on bovine spermatozoa using immunological and biochemical techniques to compare the protein profiles of X and Y chromosome-bearing sperm populations separated by fluorescence-activated cell sorting.

Currently, the only successful method for separating X and Y chromosome-bearing spermatozoa is fluorescence-activated cell sorting. Although effective, this technique is of limited usefulness to the animal breeding industry as it cannot produce the large volumes of sexed spermatozoa needed for artificial insemination. An attractive alternative would be to identify an immunological marker confined to one sperm type and, therefore, significant scientific effort has been expended in examining antibodies that appear to recognize approximately 50% of spermatozoa in an ejaculate. However, no sex-specific antigens have yet been identified from spermatozoa. Using the opportunity afforded by the development of sperm separation by fluorescence-activated cell sorting, we have made a thorough search for differences between X and Y chromosome-bearing bull spermatozoa using both biochemical and immunological methods. Techniques for radiolabelling surface membrane proteins, in conjunction with SDS-PAGE, failed to show any differences between populations. Similarly, a wide range of monoclonal antibodies raised to ejaculated, cauda epididymidal and testicular spermatozoa failed to distinguish between the X and Y chromosome-bearing spermatozoa. Only after analysis by high resolution two-dimensional SDS-PAGE was an indication obtained that X-specific proteins occur. However, these proteins are not associated with the surface membrane and further work is necessary to confirm their association with the X chromosome and to characterize them more fully. Our inability to detect sex-specific differences in sperm surface antigenicity suggests that further work on this immunological approach to semen sexing is unlikely to be profitable.

Animals↗

MR imaging findings in anterior cruciate ligament reconstruction: evaluation of notchplasty.

OBJECTIVE: Notchplasty, resection of bone from the roof and lateral side of the inter-condylar notch, is frequently performed during anterior cruciate ligament (ACL) reconstruction to avoid abrasion or deflection of the ACL graft by the femur (graft impingement). Graft impingement can develop months after the initial reconstruction despite adequate notchplasty. Such impingement has recently been attributed to fibrocartilage overgrowth of the notchplasty site. The objectives of this study were to evaluate the MR appearance of the notchplasty site immediately after surgery and 6 months later and to investigate whether cartilage overgrowth of the notchplasty site can be detected with MR imaging. SUBJECTS AND METHODS: Thirty-three patients who underwent bone-tendon-bone autograft ACL reconstruction had MR scans of the intercondylar notch 6 months after surgery. Twenty-five of these patients also had MR scans in the immediate postoperative period. The appearance of the notchplasty site and evidence for cartilage overgrowth of the notchplasty site were evaluated. Arthroscopic correlation was available for six patients. RESULTS: On MR images, the margins of the notchplasty site were identified in all patients. Contour of the notchplasty site along the lateral notch wall was frequently concave toward the notch, a finding not commonly seen in an unoperated notch. Six months later, the shape of the notchplasty site had not changed, but evidence for recortication of the notchplasty site (seen as a layer of signal void 0.5-1.5 mm in thickness over the previously exposed cancellous bone) was seen in 94% of the patients. Additionally, a second layer of signal void, 1-5 mm in thickness with signal intensity identical to that of hyaline cartilage, was seen overlying the notchplasty site in 64% of patients. Arthroscopic correlation available in six patients suggested that this second layer represented fibrocartilage overgrowth of the notchplasty site. CONCLUSION: Characteristic changes of the intercondylar notch after notchplasty can be seen on MR images. This preliminary study also suggests that a thin layer of cortical bone forms over the notchplasty site in most patients within 6 months of surgery. Perhaps more significantly, overgrowth of the notchplasty site by fibrocartilage may also be detected in some patients. Further experience is needed to determine whether MR imaging is a useful method for identifying cartilage overgrowth after notchplasty.

Adolescent↗

Experimental Results with the Multi-Linkª Stent in a Porcine Model.

OBJECTIVES: The purpose of this study was to assess the delivery characteristics and the vascular response to placement of the Multi-Linkª stent in normal porcine coronary arteries. BACKGROUND: The Multi-Link stent is a balloon expandable stainless steel stent with an interconnected corrugated ring structure designed to provide a high degree of compressive resistance while preserving longitudinal flexibility. The placement characteristics and vascular response to this stent in normal porcine coronary arteries has not been characterized. METHODS: We tested the delivery characteristics and vascular response to the Multi-Link stent in 19 normolipemic miniature swine. Quantitative coronary angiography was used to define stent performance characteristics such as stent expansion and recoil. Histologic assessment of the stented arteries was used to evaluate the acute and chronic vascular response to stent placement. RESULTS: Thirty-five of thirty-five stents (100%) were successfully implanted in the left anterior descending (n = 14), left circumflex (n = 8) or right (n = 13) coronary arteries of nineteen swine. The baseline angiographic mean lumen diameter of the stented coronary segment was 3.41 +/- 0.32 mm and increased to 3.53 +/- 0.33 mm (p < 0.001) after stent placement. The balloon inflated stent diameter was 3.61 +/- 0.36 mm with minimal recoil to a final minimal lumen diameter of 3.53 +/- 0.33 mm after implant (p = 0.001). Linear regression analysis revealed that the percent stent recoil had a significant positive correlation with the stent to artery ratio or the degree of stent over-sizing (r = 0.67; p < 0.0001). Angiographic and histologic follow-up at 72 hours (n = 9), 14 days (n = 12) and 56 days (n = 12) demonstrated that all stents were patent without evidence of migration, intraluminal filling defect or side-branch occlusion. On histology, there was rare evidence of stent-induced deep arterial wall injury such as rupture of the internal elastic lamina and medial laceration. There was no significant difference in the mean injury score observed on day 3 (0.23 +/- 0.22), 14 (0.35 +/- 0.28) or 56 (0.36 +/- 0.27) after implant (p = 0.27). On day 3, the mean thrombus thickness overlying the stent wires was 70 +/- 98µ. The mean neointimal area was similar at 14 and 56 days after implant (1.63 +/- 1.25 mm2 versus 1.78 +/- 0.68 mm2, p = 0.54). CONCLUSIONS: The MULTI-LINK stent easily tracked the coronary arteries and deployed reliably in this experimental model. The multiple interconnected ring geometry of the stent provides adequate compressive resistance, longitudinal flexibility and uniform coverage of the arterial wall throughout the length of the endoprothesis. The stent has acceptable blood and tissue biocompatibility in normal porcine coronary arteries. Oversizing this stent (>10 percent) may have a theoretical disadvantage resulting in a proportionally higher degree of stent recoil. The results of clinical trials will determine if the design features of the Multi-Link stent favorably impact on procedural outcome or long-term patency.

Journal Article↗

General practitioners' views on the over-the-counter availability of H2-antagonists.

BACKGROUND: In recent years there has been a trend towards increasing the number of drugs that are available over the counter (OTC) without prescription. Simultaneously, community pharmacists have been encouraged to develop and extend their role. General practitioners (GPs) have been shown to have some reservations about these developments. A group of drugs widely used in general practice, the H2-antagonists, have recently become available OTC. AIM: To examine GPs' attitudes towards community pharmacists dispensing H2-antagonists over the counter (OTC) without prescription. METHOD: Postal questionnaire to a sample of GPs from inner and outer London, Surrey, Kent, Hampshire, Northumberland, Newcastle upon Tyne and Leicestershire. RESULTS: Of 850 questionnaires sent, 515 were returned, an overall response rate of 60.5%. Fifty four per cent of respondents agreed that cimetidine should be available over the counter for dyspepsia in adults under 45 years not responsive to antacids. Ninety per cent of respondents were aware that H2-antagonists had been deregulated. Most general practitioners learned about the deregulation from professional journals. Very few GPs stated they had changed their prescribing practice since H2-antagonists became available OTC. The high cost to the patient of the OTC product was the most frequently mentioned reason why respondents did not encourage their patients to switch from prescription to OTC H2-antagonists. Worries and concerns regarding the OTC availability of H2-antagonists included masking serious conditions, missed diagnosis, loss of control by the GP and the potential for inappropriate use by patients. CONCLUSIONS: Since 1990, there has been a large increase in GPs support for the OTC availability of cimetidine. However, according to their stated behaviour, the reclassification of H2-antagonists does not seem to have changed GPs' prescribing practice, and few appear to be recommending that their patients buy them over the counter.

Adult↗