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Biomedical subjects

S L Smith

Publications and source records attributed to S L Smith.

At least 55 records · Page 3Linked to original sources

Clinical impact of ex vivo differentiated myeloid precursors after high-dose chemotherapy and peripheral blood progenitor cell rescue.

The infusion of ex vivo differentiated myeloid precursors may be able to shorten the period of obligatory neutropenia after high-dose chemotherapy and peripheral blood progenitor cell rescue by providing cells capable of differentiating to mature neutrophils within days of infusion. To test this hypothesis, 21 female patients with metastatic breast cancer underwent progenitor cell mobilization with cyclophosphamide, etoposide and G-CSF. CD34+ cells from one to two leukapheresis products were isolated and placed in suspension culture with a serum-free growth medium supplemented with PIXY321. The cultures were maintained for 12 days with subcultures initiated on day 7. The remaining leukapheresis products were cryopreserved in an unmanipulated state. Forty-eight hours after completing high-dose cyclophosphamide, thiotepa and carboplatin, the cryopreserved progenitors were infused, followed 1 to 24 h later by infusion of the differentiated myeloid precursors. In one patient, the cultured cells were labeled with Indium-111 with nuclear imaging performed up to 48 h post infusion. The differentiated myeloid precursors were suitable for infusion in 17 of the patients with a median 13-fold expansion of total nucleated cells. A range of 5.6 to 1066 x 10(7) nucleated cells were infused. Morphologically the cells were predominantly of myeloid lineage (63%) with a median 41% of the cells expressing CD15. No untoward effects were noted with the infusion of the cultured cells. The median days to neutrophil and platelet recovery were 8 and 10 days, respectively. There was a significant relationship (r = 0.67, P = 0.007) between the dose of differentiated myeloid precursors (CD15+ cells) and the depth and duration of neutropenia; a similar relationship, however, was also observed with the dose of cryopreserved CD34+ cells. After infusion of the radiolabeled myeloid precursors, a pattern of distribution similar to radio-labeled granulocytes was noted with uptake detected initially in the lungs and subsequently the reticulo-endothelial system. The impact of differentiated myeloid precursors on neutropenia as an adjunct to high-dose chemotherapy and peripheral blood progenitor cell rescue remains unclear from this study. Further study with controlled doses of cryopreserved progenitors and escalating doses of differentiated myeloid precursors is required.

Adult↗

The role of the plain radiograph and renal tract ultrasound in the management of children with renal tract calculi.

AIMS: The aim of this retrospective study was to assess the relative efficacy of plain abdominal radiographs and detailed renal tract ultrasound (US) examination in the diagnosis and follow-up of children with renal tract calculi. METHODS: The records and imaging studies of 28 paediatric patients who had presented with proven renal tract calculi over a period of 5 years were examined. RESULTS: In 23 (82%) patients, US was the first investigation. All these patients also had plain radiographs. Plain radiographs were the first investigation in five (18%) patients. All renal calculi (100%) visible on plain films were demonstrated on US. Furthermore, detailed US often provided other clinically significant findings that were not apparent on plain films. CONCLUSION: As a result of this study it is recommend that detailed US should be the investigation of choice in children with suspected renal tract calculi.

Adolescent↗

Variation in the wear rate during the life of a total hip arthroplasty: a simulator and retrieval study.

The limitation of wear is fundamental to the optimization of total hip arthroplasty longevity. The maintenance of the supersmooth femoral head surface is considered to be paramount in maximizing prosthesis life expectancy. Ex vivo studies have failed to substantiate a relationship between roughness and the clinical wear factor, however. A hip simulator wear study was undertaken to investigate this contradiction. Three explanted femoral heads were articulated for 5 million cycles against new acetabular liners. The simulator wear rate was 5 times the ex vivo value. This difference can be explained only if the explant head roughness was not that which existed for most of the joint's life. The relationship between surface roughness and wear deduced for simulator testing is substantially different from that of unidirectional wear screening methods. The multiphasic nature of wear in cementless joints has been illustrated: a wear-in period, followed by a steady-state phase, until a head-roughening event causes a rapid wear period.

Arthroplasty, Replacement, Hip↗

Increased plasma beta-hydroxybutyrate, preserved cerebral energy metabolism, and amelioration of brain damage during neonatal hypoxia ischemia with dexamethasone pretreatment.

Dexamethasone (DEX) pretreatment has been shown to be neuroprotective in a neonatal rat model of hypoxia ischemia (HI). The exact mechanism of this neuroprotection is still unknown. This study used 31P nuclear magnetic resonance spectroscopy to monitor energy metabolism during a 3-h episode of HI in 7-d-old rat pups in one of two groups. The first group was pretreated with 0.1 mL saline (i.p.) and the second group was treated with 0.1 mL of 0.1mg/kg DEX (i.p.) 22 h before HI. Animals pretreated with DEX had elevated nucleoside triphosphate and phosphocreatine levels during HI when compared with controls. Saline-treated animals had significant decreases in nucleoside triphosphate and phosphocreatine and increases in inorganic phosphate over this same period. 31P nuclear magnetic resonance data unequivocally demonstrate preservation of energy metabolism during HI in neonatal rats pretreated with DEX. Animals pretreated with DEX had little or no brain damage following 3 h of HI when compared with matched controls, which experienced severe neuronal loss and cortical infarction. These same pretreated animals had an increase in blood beta-hydroxybutyrate levels before ischemia, suggesting an increase in ketone bodies, which is the neonate's primary energy source. Elevation of ketone bodies appears to be one of the mechanisms by which DEX pretreatment provides neuroprotection during HI in the neonatal rat.

3-Hydroxybutyric Acid↗

Simplified motion and loading compared to physiological motion and loading in a hip joint simulator.

Two wear tests were conducted using the Durham Hip Joint Wear Simulator to investigate the effects of simplified motion and loading on ultra-high molecular weight polyethylene (UHMWPE) acetabular cup wear rates. Bovine serum was used as a lubricant and a gravimetric technique was used to measure wear. The first wear test duration was 7.1 x 10(6) cycles and investigated the effect of simplified loading. This was achieved by using full physiological motion and loading for the first 5 x 10(6) cycles of the test, then physiological motion with simplified loading for the final 2.1 x 10(6) cycles of the wear test. The UHMWPE acetabular cup wear rates using full physiological motion and loading were 32.2 and 51.7 mm3/10(6) cycles against zirconia and CoCrMo femoral heads respectively. Using simplified loading the cup wear rates were 30.1 and 49.2 mm3/10(6) cycles against zirconia and CoCrMo respectively which was not significantly different from wear rates with physiological loading. The effect of simplified motion was investigated in a second wear test of 5.0 x 10(6) cycles duration. Physiological loading was applied across the prosthesis with physiological motion in the flexion/extension plane only. Mean wear of the acetabular component dropped to 0.197 mm3/10(6) cycles. The surfaces of all the acetabular cups were subject to gross examination, optical microscopy and scanning electron microscopy. No notable difference was observed between the cups subjected to physiological motion and loading and those subjected to simplified loading. The cups worn with a single plane of motion had a much smaller worn area and a notable difference in surface features to the other cups. Simplifed loading is therefore an acceptable simplification in simulator testing but simplifying motion to the flexion/extension plane axis only is unacceptable.

Acetabulum↗

Health promotion versus disease and care: failure to establish "blissful clarity" in British nurse education and practice.

An evaluation which involved documentary analysis, observation and interviews with teachers, students and nurses in four educational institutions, revealed that the interpretation and implementation of a philosophy of health in nursing in the UK has been variable. A small but influential group of teachers saw health as the basis for the curriculum and the way forward for nursing. The new Project 2000 health-based curriculum led some participants to reassess their conception of nursing, but disease and care of the sick remained uppermost. Trained hospital nurses in particular continued to view nursing as primarily concerned with disease treatment. The care model associated with 'New Nursing', rooted in communication and interpersonal relationships, was also apparent particularly among pre- and post-registration students. Health was operationalised as both health education and health promotion ranging from individualised information giving and disease prevention to more participatory forms based on equity and empowerment. Participants' responses to the introduction of health in the curriculum were categorised in one of four ways: pessimism, partisanship, fanschen (to turn over) or marketisation. Their response depended on whether they viewed health as the central nursing philosophy rather than disease or care. On the basis of our findings we propose that these responses give rise to four policy choices for nurses at an individual and group level.

Education, Nursing↗

The use of latanoprost 0.005% once daily to simplify medical therapy in patients with primary open-angle glaucoma or ocular hypertension.

PURPOSE: To evaluate the use of latanoprost 0.005% given once daily to simplify a patient's glaucoma medical regimen. METHODS: We reviewed 527 charts of which we included 61 patients (61 eyes) with either ocular hypertension or primary open-angle glaucoma who were prescribed latanoprost for the purpose of simplifying their glaucoma medical regimen. The successful substitution of latanoprost was defined as a reduction in the number of dosages given daily with the maintenance of intraocular pressure for at least three months no higher than 2 mmHg from the previous medical regimen. RESULTS: This study showed that 43 of 61 patients (70.4%) had latanoprost substituted allowing for fewer dosages per day. Following the substitution the intraocular pressure in the success group fell from 22.5+/-5.9 mmHg to 18.3+/-3.8 mmHg (p<0.001) over an average follow-up of 6.6+/-1.9 months. The total number of dosages per day in the success group fell from 4.8+/-2.4 to 1.7+/-1.3 at exit (p<0.001). Twenty-two patients had one medicine, 14 patients two, and seven patients three medicines discontinued after latanoprost was added. Reasons for failure after the substitution were ineffectiveness of latanoprost (n=11) or an adverse event (n=7). No trends in the number or types of medicines at baseline discontinued were observed in the success or failure groups. CONCLUSION: This study shows that latanoprost 0.005% once daily can be substituted for one or more medicines in the majority of ocular hypertension and primary open-angle glaucoma patients to simplify the medical regimen.

Aged↗

Latanoprost 0.005% and anterior segment uveitis.

PURPOSE: To evaluate the association of latanoprost with anterior chamber uveitis in glaucoma patients. METHODS: We retrospectively reviewed 527 charts in latanoprost treated patients with: no prior uveitis (Group 1); prior uveitis but were inactive at the time of the study (Group 2); and active uveitis (Group 3). RESULTS: In Group 1 five (1.0%) of 505 patients developed uveitis after beginning latanoprost. The uveitis was trace to 1+ cell in severity and delayed in onset 99.8+/-73.9 days In Group 2 three of 13 (23.1%) patients developed delayed uveitis (trace to 1+ cell). In Group 3 zero of nine (0%) patients had worsened inflammation and the intraocular pressure remained unchanged (22.8+/-7.8 mmHg to 22.0+/-7.3 mmHg) after beginning latanoprost (p=0.38). CONCLUSION: In patients without a prior history a mild delayed uveitis with latanoprost treatment may develop rarely. In patients with a uveitis history, a mild delayed exacerbation potentially may occur and the intraocular pressure may not be decreased in active uveitis.

Aged↗

Analysis of pressure achieved by various materials used for pressure dressings.

BACKGROUND: To minimize the risk of complications, pressure dressings are frequently applied to wounds. The actual pressures yielded by different dressing materials and application techniques have not been documented. OBJECTIVE: To measure and compare pressures produced using various types of dressing tapes with and without a gauze roll. METHODS: An infant blood pressure cuff was adapted for use in a pressure dressing model. Investigators independently applied four strips of each of five different types of tape to the cuff when it was located in three settings: a hard inanimate surface, a subject's distal volar forearm, and the subject's forehead. RESULTS: Foam and plastic tapes produced more pressure under a simple dressing than three other commonly used tapes. Higher, more consistent pressures were achieved on the forearm than the forehead. Adding a gauze roll to the dressing consistently increased the pressure. CONCLUSION: The experimental model demonstrated substantial differences in pressures yielded by various pressure dressing materials.

Analysis of Variance↗

Is mammography of value in women with disseminated cancer of unknown origin?

Mammography is often requested to try to identify occult primary breast carcinoma in women with metastatic cancer of unknown primary site. This study aimed to investigate whether mammography is of use in these patients in identifying the breast as the origin of the metastatic disease. Thirty-one women with a working diagnosis of metastatic cancer underwent mammography in an attempt to determine the primary site. None of these women had a palpable breast mass. The site of presentation, pathological type of tumour, site of origin, and benefit of mammography and mammography-provoked biopsy were clarified for each patient. The patients were also followed up to determine survival. The commonest sites of presentation were lung (45%), lymph nodes (19%) and abdomen (16%). The primary sites of these cancers were identified with confidence in 27 patients (87%). The commonest known primary tumour sites were lung (45%), breast (16%) and ovary (16%). Abnormal mammograms were detected in four patients (13%), but three of these did not have breast cancer. In one, the site of origin remained indeterminate, as either breast or lung. Five (16%) had a confident diagnosis of breast carcinoma; all of these women had normal mammograms. We conclude that mammography in women presenting with metastatic disease from an unknown primary site is unhelpful and is not recommended. Furthermore, we could not demonstrate its value in women presenting with axillary lymphadenopathy.

Adult↗

The use of latanoprost 0.005% once daily and its effect on intraocular pressure as primary or adjunctive therapy.

The purpose of this study was to evaluate differences in efficacy and safety of latanoprost as monotherapy compared to adjunctive therapy in primary open-angle glaucoma. We reviewed records of 527 patients who were treated with latanoprost as mono- or adjunctive therapy to reduce the intraocular pressure. Each patient was treated at least three months unless they were discontinued due to an adverse event or lack of efficacy. In the monotherapy group (n=49) baseline intraocular pressure of 23.6+/-5.2 mm Hg fell to 18.4+/-4.3 mm Hg after 4.4+/-2.0 months of follow-up; in the adjunctive therapy group (n=39) baseline intraocular pressure of 21.8+/-5.7 mm Hg fell to 16.7+/-4.6 mm Hg following 4.3+/-1.8 months of therapy which was a similar change from baseline for both groups (P > 0.9). No differences were noted in the class or number of medicines to which latanoprost could be added including: beta-blockers, alpha-agonists and topical carbonic anhydrase inhibitors. The reasons for failure with monotherapy were mostly adverse events (10/15 patients) and with adjunctive therapy lack of efficacy (14/16 patients). Latanoprost is similarly effective as monotherapy and as an adjunctive agent in reducing the intraocular pressure. Latanoprost can be added successfully to a variety of classes of glaucoma medicines used commonly as adjunctive therapy.

Adrenergic alpha-Agonists↗

A review of major factors contributing to errors in human hair association by microscopy.

Forensic hair examiners using traditional microscopic comparison techniques cannot state with certainty, except in extremely rare cases, that a found hair originated from a particular individual. They also cannot provide a statistical likelihood that a hair came from a certain individual and not another. There is no data available regarding the frequency of a specific microscopic hair characteristic (i.e., microtype) or trait in a particular population. Microtype is a term we use to describe certain internal characteristics and features expressed when observing hairs with unpolarized transmitted light. Courts seem to be sympathetic to lawyer's concerns that there are no accepted probability standards for human hair identification. Under Daubert, microscopic hair analysis testimony (or other scientific testimony) is allowed if the technique can be shown to have testability, peer review, general acceptance, and a known error rate. As with other forensic disciplines, laboratory error rate determination for a specific hair comparison case is not possible. Polymerase chain reaction (PCR)-based typing of hair roots offer hair examiners an opportunity to begin cataloging data with regard to microscopic hair association error rates. This is certainly a realistic manner in which to ascertain which hair microtypes and case circumstances repeatedly cause difficulty in association. Two cases are presented in which PCR typing revealed an incorrect inclusion in one and an incorrect exclusion in another. This paper does not suggest that such limited observations define a rate of occurrence. These cases illustrate evidentiary conditions or case circumstances which may potentially contribute to microscopic hair association errors. Issues discussed in this review paper address the potential questions an expert witness may expect in a Daubert hair analysis admissibility hearing.

Adult↗

Acyclovir is phosphorylated by the human cytomegalovirus UL97 protein.

Acyclovir (ACV) has shown efficacy in the prophylactic suppression of human cytomegalovirus (HCMV) reactivation in immunocompromised renal transplant patients without the toxicity associated with ganciclovir (GCV). The HCMV UL97 gene product, a protein kinase, is responsible for the phosphorylation of GCV in HCMV-infected cells. This report provides evidence for the phosphorylation of ACV by UL97. Anabolism studies with the HCMV wild-type strain AD169 and with recombinant mutants derived from marker transfer experiments performed by using mutant UL97 DNA from both clinical isolates and a laboratory-derived strain resistant to GCV showed that mutations in the UL97 gene cripple the ability of recombinant virus-infected cells to anabolize both GCV and ACV. These mutant UL97 recombinant viruses were less susceptible to both GCV and ACV than was the wild-type strain. A recombinant herpes simplex virus type 1 strain, in which the thymidine kinase gene is deleted and the UL13 gene is replaced with the HCMV UL97 gene, was able to induce the phosphorylation of ACV in infected cells. Finally, purified UL97 phosphorylated both GCV and ACV to their monophosphates. Our results indicate that UL97 promotes the selective activity of ACV against HCMV.

Acyclovir↗

Stimulation of strontium accumulation in linoleate-enriched Saccharomyces cerevisiae is a result of reduced Sr2+ efflux.

The influence of modified plasma membrane fatty acid composition on cellular strontium accumulation in Saccharomyces cerevisiae was investigated. Growth of S. cerevisiae in the presence of 1 mM linoleate (18:2) (which results in 18:2 incorporation to approximately 70% of total cellular and plasma membrane fatty acids, with no effect on growth rate) yielded cells that accumulated Sr2+ intracellularly at approximately twice the rate of S. cerevisiae grown without a fatty acid supplement. This effect was evident over a wide range of external Sr2+ concentrations (25 microM to 5 mM) and increased with the extent of cellular 18:2 incorporation. Stimulation of Sr2+ accumulation was not evident following enrichment of S. cerevisiae with either palmitoleate (16:1), linolenate (18:3) (n-3 and n-6 isomers), or eicosadienoate (20:2) (n-6 and n-9 isomers). Competition experiments revealed that Ca2+- and Mg2+-induced inhibition of Sr2+ accumulation did not differ between unsupplemented and 18:2-supplemented cells. Treatment with trifluoperazine (TFP) (which can act as a calmodulin antagonist and Ca2+-ATPase inhibitor), at a low concentration that precluded nonspecific K+ efflux, increased intracellular Sr2+ accumulation by approximately 3.6- and 1.4-fold in unsupplemented and 18:2-supplemented cells, respectively. Thus, TFP abolished the enhanced Sr2+ accumulation ability of 18:2-supplemented cells. Moreover, the rate of Sr2+ release from Sr2+-loaded fatty acid-unsupplemented cells was found to be at least twice as great as that from Sr2+-loaded 18:2-enriched cells. The influence of enrichment with other fatty acids on Sr2+ efflux was variable. The results reveal an enhanced Sr2+ accumulation ability of S. cerevisiae following 18:2-enrichment, which is attributed to diminished Sr2+ efflux activity in these cells.

Calcium↗

A multifunctional ATP-binding cassette transporter system from Vibrio cholerae transports vibriobactin and enterobactin.

Vibrio cholerae uses the catechol siderophore vibriobactin for iron transport under iron-limiting conditions. We have identified genes for vibriobactin transport and mapped them within the vibriobactin biosynthetic gene cluster. Within this genetic region we have identified four genes, viuP, viuD, viuG and viuC, whose protein products have homology to the periplasmic binding protein, the two integral cytoplasmic membrane proteins, and the ATPase component, respectively, of other iron transport systems. The amino-terminal region of ViuP has homology to a lipoprotein signal sequence, and ViuP could be labeled with [(3)H]palmitic acid. This suggests that ViuP is a membrane lipoprotein. The ViuPDGC system transports both vibriobactin and enterobactin in Escherichia coli. In the same assay, the E. coli enterobactin transport system, FepBDGC, allowed the utilization of enterobactin but not vibriobactin. Although the entire viuPDGC system could complement mutations in fepB, fepD, fepG, or fepC, only viuC was able to independently complement the corresponding fep mutation. This indicates that these proteins usually function as a complex. V. cholerae strains carrying a mutation in viuP or in viuG were constructed by marker exchange. These mutations reduced, but did not completely eliminate, vibriobactin utilization. This suggests that V. cholerae contains genes in addition to viuPDGC that function in the transport of catechol siderophores.

ATP-Binding Cassette Transporters↗

Laparoscopic antireflux surgery--It's a wrap!

The surgical management of gastroesophageal reflux disease has been simplified by the availability of minimally invasive techniques to treat this condition. The indications and selection of patients remain the same as for open surgery and initial results with laparoscopic antireflux surgery show long-term results equal to, or better than open procedure. These procedures are technically demanding requiring surgeons skilled in advanced laparoscopy. The evaluation of patients, selection of patients for surgery, surgical techniques and anticipated outcomes are discussed.

Female↗

Evaluation of a hip joint simulator.

To evaluate the functioning of the Durham hip joint wear simulator, the wear rates of ultra high molecular weight polyethylene (UHMWPE) and polytetrafluoroethylene (PTFE) acetabular cups articulating against 22 mm diameter cobalt-chromium-molybdenum (CoCrMo) femoral heads were studied. A wear test was conducted in a lubricant of distilled water at 37 degrees C for a duration of 4.8 million cycles. The average penetration rate for the CoCrMo femoral heads against UHMWPE acetabular cups was 0.03 mm/10(6) cycles, while penetration rate for PTFE cups was some twenty times greater. These results are of a similar order of magnitude to other simulator studies in distilled water and are in a similar ratio to clinical data.

Acetabulum↗