Search PubMedSearch

Biomedical subjects

P Campbell

Publications and source records attributed to P Campbell.

At least 19 recordsLinked to original sources

Quantitative structure-activity relationship (QSAR) analysis of surfactants influencing attachment of a Mycobacterium sp. to cellulose acetate and aromatic polyamide reverse osmosis membranes.

A series of 23 neutral, anionic, and zwitterionic surfactants were tested at a concentration of 0.1% wt/vol for their influence on attachment of a Mycobacterium sp. to cellulose acetate (CA) and polyamide (PA) reverse osmosis (RO) membranes. Four cell attachment bioassays were used: (1) semiconcurrent addition of surfactant and bacteria to RO coupons (standard assay); (2) surfactant pretreatment of RO membranes (membrane pretreatment assay); (3) surfactant treatment of adsorbed cells (detachment assay); and (4) surfactant pretreatment of mycobacteria (cell pretreatment assay). Seventeen surfactants inhibited attachment to PA membranes, whereas 15 inhibited attachment to CA in standard assays and, in 13 cases, the same surfactant inhibited attachment to both PA and CA. Despite greater cell attachment to PA than CA, surfactants were typically more effective in the former membrane system. More surfactants were effective in impairing cell attachment than in promoting detachment and a number enhanced attachment in membrane pretreatment assays, suggesting surface modification of RO membranes. Cell pretreatment inhibited attachment to CA membranes, suggesting the bacterial surface was also a target for detergent activity. Multivariate regression and cluster analyses indicated that critical micellar concentration (CMC) was positively correlated with Mycobacterium attachment in CA and PA standard assays. Surfactant dipole moment and octanol/water partitioning (LogP) also contributed to detergent activity in the PA system, whereas dipole moment, molecular topology (i.e., connectivity indices), and charge properties influenced activity in the CA system. Influential variables in membrane pretreatment assays included the LogP, topology indices, and charge properties, whereas CMC played a diminished role. Surfactant dipole moment was most influential in CA membrane detachment assays. Increasing system ionic strength by LiBr addition strengthened inhibition of cell attachment to CA membranes by dodecylbenzene sulfonic acid (DBSA) and promoted DBSA adsorption to CA surfaces as indicated by attenuated total reflection Fourier-transform infrared spectrometry. Results indicate that inhibition of bacterial attachment to RO membranes may be maximized by manipulating surfactant molecular structure to optimize surface adsorption behavior.

Bacterial Adhesion

Development of an extremely wear-resistant ultra high molecular weight polyethylene for total hip replacements.

Osteolysis induced by ultra high molecular weight polyethylene wear debris is one of the primary factors limiting the lifespan of total hip replacements. Crosslinking polyethylene is known to improve its wear resistance in certain industrial applications, and crosslinked polyethylene acetabular cups have shown improved wear resistance in two clinical studies. In the present study, crosslinked polyethylene cups were produced by two methods. Chemically crosslinked cups were produced by mixing a peroxide with ultra high molecular weight polyethylene powder and then molding the cups directly to shape. Radiation-crosslinked cups were produced by exposing conventional extruded ultra high molecular weight polyethylene bar stock to gamma radiation at various doses from 3.3 to 100 Mrad (1 Mrad = 10 kGy), remelting the bars to extinguish residual free radicals (i.e., to minimize long-term oxidation), and then machining the cups by conventional techniques. In hip-joint simulator tests lasting as long as 5 million cycles, both types of cross-linked cups exhibited dramatically improved resistance to wear. Artificial aging of the cups by heating for 30 days in air at 80 degrees C induced oxidation of the chemically crosslinked cups. However, a chemically crosslinked cup that was aged 2.7 years at room temperature had very little oxidation. Thus, whether substantial oxidation of chemically crosslinked polyethylene would occur at body temperature remains unclear. The radiation-crosslinked remelted cups exhibited excellent resistance to oxidation. Because crosslinking can reduce the ultimate tensile strength, fatigue strength, and elongation to failure of ultra high molecular weight polyethylene, the optimal crosslinking dose provides a balance between these physical properties and the wear resistance of the implant and might substantially reduce the incidence of wear-induced osteolysis with total hip replacements.

Arthroplasty, Replacement, Hip

Effect of molecular weight, calcium stearate, and sterilization methods on the wear of ultra high molecular weight polyethylene acetabular cups in a hip joint simulator.

Orthopaedic surgeons must currently choose from several types of ultra high molecular weight polyethylene acetabular cups that differ in their material properties and in the methods used for their sterilization. Information on the wear resistance of these different cups may help in the selection process. This study included two separate tests for wear run on a hip simulator to investigate the effect of molecular weight, calcium stearate, and sterilization methods on the wear resistance of ultra high molecular weight polyethylene acetabular cups. Test 1 revealed nearly identical wear rates for acetabular cups with molecular weights in two distinct ranges, as well as for cups with molecular weights in the same range but with or without calcium stearate added. In Test 2, cups that were sterilized in air with gamma irradiation exhibited lower rates of wear than those sterilized with ethylene oxide, presumably due to the crosslinking induced by the irradiation. In addition, cups that were irradiated while packed in a partial vacuum to minimize oxygen absorbed in the surface layer initially showed lower rates of wear than those irradiated in air, with the wear rates becoming similar as wear penetrated the more oxidized surface layer and the more crosslinked subsurface region. Because these tests were run a few months after the irradiation, the potential effects of long-term oxidation of any residual free radicals in the irradiated materials could not be taken into account. After artificial aging to accelerate oxidative degradation of the materials, the wear rates could be markedly different. Analyses performed after wear indicated that the irradiated (i.e., crosslinked) cups exhibited a smaller proportion of, as well as shorter, fibrils in the wear debris and an increased crystallinity and melting temperature and that gamma irradiation in the low-oxygen environment reduced the level of oxidation and increased the level of crosslinking in the surface region of the cups.

Acetabulum

The importance of graft blood flow and peripheral outflow resistance for early patency in infrainguinal arterial reconstructions.

BACKGROUND: At present, the importance of functional parameters as determinants for graft patency is under debate. Therefore, in our institution a prospective study was undertaken to evaluate the influence of graft blood flow as well as the currently applied methods for outflow resistance measurement on early (< or = 30 days) graft outcome. PATIENT AND METHODS: 101 arterial revascularisations with infrageniculate graft insertion were entered into this study. After having verified the morphological integrity of the reconstruction, during temporary inflow occlusion total outflow resistance (TOR) was determined as a pressure/flow relationship by perfusion of the graft with saline (flow rates 25, 50, 100, 150 ml/min before and after papaverine) while simultaneously recording pressure generated at the distal anastomosis. In addition, after restoration of blood flow, flow index (FI) was calculated in an analogous way from the TBF through the graft and the respective mean distal anastomotic pressure. Graft patency at 30 days was determined by Duplex ultrasound. RESULTS: Functional parameters were found to be unable to differentiate between patent and failed reconstructions during the 30 day period: The mean TORaveraged values amounted to 722.5 (SD = 310) in patent and 735.9 (SD = 228.1) mPRU in occluded bypasses (T-value = 0.1681; n.s.). The corresponding figures were 176.8 (SD = 94.2) and 196.4 (SD = 93.6) ml/min for TBF (T-value = 0.7342; n.s.) and were 0.53 (SD = 0.34) and 0.45 (SD = 0.25) PRU for FI (T-value = 0.8905; n.s.). Using multiple logistic regression analysis functional parameters showed no influence on graft patency while graft length and the necessity for intraoperative graft modification emerged to be significant determinants of early graft outcome (R2 adjusted = 0.46; p = 0.006). CONCLUSION: The results of our study suggest that neither blood flow nor the presently used methods to assess outflow resistance are relevant prognostic factors for early (< or = 30 days) graft performance.

Adult

Syngeneic stem cell transplantation for HIV-related lymphoma.

The treatment of human immunodeficiency virus (HIV)-related lymphoma is beset by a number of therapeutic limitations. High-dose chemotherapy followed by peripheral blood stem cell transplantation (PBSCT) for relapsed disease is one option, but may be compromised by unacceptable treatment-related morbidity and mortality. We describe an HIV-positive male with relapsed immunoblastic non-Hodgkin's lymphoma (NHL) who successfully received salvage chemotherapy followed by a syngeneic PBSCT from his HIV-negative (hepatitis C positive) brother. At 15 months post-transplant he remains in complete remission with low-level HIV viral load, an improved CD4 lymphocyte count and absent anti-hepatitis C antibodies. We believe selected patients with relapsed HIV-related NHL should be considered for high-dose therapy.

Adult

In vitro activities of four xyloglucan endotransglycosylases from Arabidopsis.

Xyloglucan endotransglycosylases (XETs) are encoded by a gene family in Arabidopsis thaliana. These enzymes modify a major structural component of the plant cell wall, xyloglucan, and therefore may influence plant growth and development. We have produced four Arabidopsis XETs (TCH4, Meri-5, EXGT and XTR9) using the baculovirus/insect cell system and compared their biochemical activities. TCH4, as previously demonstrated, and the other three proteins are capable of carrying out transglycosylation of xyloglucans. The K(m) for XLLGol acceptor oligosaccharide is in the range of 20-40 microM for all the XETs except XTR9, which has a Km of 5 microM and is significantly inhibited by high levels of XLLGol. All four enzymes are most active between pH 6.0 and 6.5. TCH4 and XTR9 have temperature optima of 18 degrees C, whereas Meri-5 and EXGT are most active at 28 and 37 degrees C, respectively. Although the activity levels of three of the XETs are not influenced by the presence of fucose on the xyloglucan polymer, XTR9 has a clear preference for non-fucosylated xyloglucan polymer. The four XETs show a marked preference for XLLGol over either XXFGol or XXXGol as acceptor oligosaccharide. All four XETs are glycosylated; however, only the activities of TCH4 and Meri-5 are affected by the removal of the N-glycan with PNGase F. These four enzymes most likely function solely as transglycosylases because xyloglucan endoglucanase activity was not apparent. Subtle differences in biochemical activities may influence the physiological functions of the distinct XETs in vivo.

Arabidopsis

Reduction in choline acetyltransferase immunoreactivity but not muscarinic-m2 receptor immunoreactivity in the brainstem of SIDS infants.

The cholinergic neurotransmitter system is vital for several brainstem functions including cardiorespiratory control and central chemosensitivity. This study has examined aspects of the cholinergic neurotransmitter system in the brainstem of sudden infant death syndrome (SIDS) and control infants. The cellular localisation and the optical density of the immunoreactivity of the cholinergic enzyme choline acetyltransferase (CHAT-IR) and the muscarinic acetylcholine receptor m2 (m2-IR) in the medulla was described in 14 SIDS and 9 control cases. There was a reduction in the number of CHAT-IR neurons in the hypoglossal nucleus (control: 71.2+/-8.3% vs SIDS: 46.1+/-5.3%) and the dorsal motor nucleus of the vagus (DMV) (control: 77.2+/-5.0% vs SIDS: 52.5+/-7.4%) and reduced optical density of CHAT-IR in the hypoglossal nucleus (control: 0.20+/-0.01 vs SIDS; 0.14+/-0.02) in SIDS infants. In contrast there were no changes in the optical density of m2-IR in the hypoglossal nucleus, the DMV, or the arcuate nucleus. Hypoplasia of the arcuate nucleus was observed in one SIDS infant. These results suggest that there is a specific defect in some cholinergic motor neurons in the medulla of SIDS infants. This could lead to abnormal control of cardiovascular and respiratory function and airway patency and may be one of the contributing factors in the etiology of SIDS.

Brain Stem

Mechanism of failure in hips with an uncemented, all polyethylene socket.

The outcome of 32 patients with 33 primary total hip replacements performed using noncemented uncoated polyethylene acetabular cups (RM cup) with cemented titanium alloy monoblock stems (STH-2 stem) was reviewed. At a mean followup of 6.3 years (range, 6 months-10 years), the failure rate was 57%, more than 14 times higher than the rate typically seen with cemented polyethylene acetabular cups used with the STH stem. Failure was characterized by rapidly progressive acetabular or femoral osteolytic lesions that resulted in extensive bone loss, often in patients who had no symptoms. In addition to the debris that typically is generated by a metal on plastic bearing couple, an abundance of polyethylene particles of submicron size were produced at the cup-bone interface. Tissues retrieved from areas of osteolysis revealed the presence of intracellular submicron polyethylene particles in macrophages. It is recommended that patients with no symptoms who have RM noncemented, uncoated acetabular cups be followed up yearly and undergo early revision surgery when faced with osteolysis to prevent extensive bone loss.

Acetabulum

Co- and/or post-translational modifications are critical for TCH4 XET activity.

TCH4 encodes a xyloglucan endotransglycosylase (XET) of Arabidopsis thaliana. XETs endolytically cleave and religate xyloglucan polymers; xyloglucan is one of the primary structural components of the plant cell wall. Therefore, XET function may affect cell shape and plant morphogenesis. To gain insight into the biochemical function of TCH4, we defined structural requirements for optimal XET activity. Recombinant baculoviruses were designed to produce distinct forms of TCH4. TCH4 protein engineered to be synthesized in the cytosol and thus lack normal co- and post-translational modifications is virtually inactive. TCH4 proteins, with and without a polyhistidine tag, that harbor an intact N-terminus are directed to the secretory pathway. Thus, as predicted, the N-terminal region of TCH4 functions as a signal peptide. TCH4 is shown to have at least one disulfide bond as monitored by a mobility shift in SDS-PAGE in the presence of dithiothreitol (DTT). This disulfide bond(s) is essential for full XET activity. TCH4 is glycosylated in vivo; glycosidases that remove N-linked glycosylation eliminated 98% of the XET activity. Thus, co- and/or post-translational modifications are critical for optimal TCH4 XET activity. Furthermore, using site-specific mutagenesis, we demonstrated that the first glutamate residue of the conserved DEIDFEFL motif (E97) is essential for activity. A change to glutamine at this position resulted in an inactive protein; a change to aspartic acid caused protein mislocalization. These data support the hypothesis that, in analogy to Bacillus beta-glucanases, this region may be the active site of XET enzymes.

Animals

Implications of early sonographic evaluation of parapneumonic effusions in children with pneumonia.

OBJECTIVE: To devise a clinically relevant grading system for the sonographic evaluation of parapneumonic effusions, and to evaluate length of hospital stay as a function of treatment approach and sonographic grades. METHODS: Chest sonograms of 46 pediatric patients diagnosed with empyemas and admitted to two medical centers in the last 8 years were retrospectively evaluated using a grading system based on the degree of fibrinous organization within the parapneumonic effusions. Hospital charts were reviewed to determine the method of treatment and length of hospital stay. Patients were divided into two treatment groups: nonoperative (n = 26) (antibiotics alone, or combined with thoracentesis, or tube thoracostomy) and operative (n = 20) (open decortication, or video thoracoscopy and pleural debridement). Patients in the nonoperative group were further subdivided into two groups: those who received antibiotics alone (n = 11) and those who received antibiotics plus nonoperative drainage thoracentesis and/or tube thoracostomy (n = 15). Within each treatment group, patients were subdivided into two ultrasound grades: low (no evidence of organization) and high (evidence of organization such as fronds, septations, or loculations). Student's t test was performed to compare the lengths of hospital stay for each of the treatment groups and ultrasound grades. RESULTS: The length of hospitalization was no different for patients with low-grade ultrasounds in the nonoperative (9.8 days) and operative groups (8.0 days). In contrast, length of hospitalization was significantly shorter for patients with high-grade sonograms in the operative group (8.6 days), when compared with the nonoperative group (16.4 days). Length of hospitalization for patients in the nonoperative group with high-grade sonograms was significantly longer (16.4 days) than for those with low-grade ultrasounds (9.8 days). Furthermore, when the nonoperative patients were divided into an antibiotics alone group and a nonoperative drainage group, the patients with low-grade sonograms had no difference in the length of hospitalization (9.0 days vs. 10.4 days), whereas those patients with high-grade sonograms in the nonoperative drainage group had a significantly longer hospitalization (19.9 days) than the antibiotics alone (high-grade) group (11.4 days). CONCLUSIONS: Patients with a low-grade sonogram had similar length of hospitalization if treated with either nonoperative or operative measures. Patients with high-grade sonograms had significantly shorter length of hospitalization when treated with decortication. Our retrospective study suggests that patients with high-grade ultrasound studies treated nonoperatively do not benefit from pleural drainage procedures or chest tube placement. This study demonstrates the usefulness of early sonographic evaluation of parapneumonic effusions. A prospective study evaluating the usefulness of sonographic assessment of severity of disease in the treatment of children with parapneumonic effusions is warranted on the basis of our retrospective data.

Adolescent

Assessment of press-fit hip femoral components retrieved at autopsy.

Eleven femurs with press-fit titanium hip components were retrieved at autopsy for clinical, radiographic, and histologic evaluation. Back-scattered electron microscopy (BEM), bone densitometry, and appositional bone index studies also were performed. The average patient age was 87 years; the average time in situ was 22 months (range: 2 to 60). All patients were functioning well and pain free. Radiographs and bone mineral density studies (BMD) showed mild proximal stress shielding in five cases. No cases of osteolysis or pedestal formation were observed. Histologic sections revealed an average of 26% bone-prosthesis contact. Bone surrounding the prosthesis appeared viable, and osteoclastic activity in the interfacial bone was minimal; the presence of macrophages and inflammatory cells was rare. The appositional bone index averaged 40%. Bone-prosthesis contact was seen consistently at the corners of the component in the multiple regions, mostly were prosthesis-endosteal cortical contact was made. BEM demonstrated intimate contact of bone with the rough titanium surface. Bone mineral density was lower in the lesser trochanter and medial proximal regions of the implanted femur than in the contralateral femur. Evidence of bone on-growth fixation in 11 femoral components suggests that cementless, stable bone fixation may be achievable in senior individuals and that "complete fit and fill," porous-coated, cementless prostheses may not be required for prosthesis stability.

Aged

Temperature dependency of the vagal chronotropic response in the young puppy: an 'environmental-autonomic interaction'.

We investigated the effects of mild hypothermia (34.3 +/- 0.2 degrees C [mean +/- SD]), hyperthermia (40.8 +/- 0.2 degrees C) and hypoxia (PaO2 = 43 +/- 4 mmHg) on the response to heart rate to continuous right vagus nerve stimulation (the 'vagal chronotropic response') in young puppies, aged 5-22 days. Puppies were anesthetized with alpha-chloralose, vagotomized and pre-treated with propranolol (1 mg/kg i.v.) and phentolamine (1 mg/kg, 1-2 mg/kg/h i.v.). Hypoxia (n = 9) did not significantly alter the resting sinus cycle length and did not alter the response of sinus cycle to a 30 s train of 8 Hz right vagal stimulation. Mild hypothermia (n = 8) increased the resting sinus cycle length by 16 +/- 4% and greatly augmented the vagal chronotropic response (from 76 +/- 27% change in the sinus cycle length (normothermia) to 155 +/- 38% (hypothermia)). Both the sinus cycle length and the vagal chronotropic response turned towards pre-hypothermia values with rewarming. Mild hypothermia also increased the negative chronotropic response to 20 micrograms/kg/min i.v. of methacholine (12 +/- 2% change in the sinus cycle length (normothermia) versus 24 +/- 14% (hypothermia)), suggesting that a postsynaptic mechanism is involved in the hypothermia-induced augmentation of the cardiac vagal chronotropic response. In contrast to hypothermia, mild hyperthermia (n = 8) decreased the resting sinus cycle length slightly (-5 +/- 5% change) and significantly attenuated the cardiac vagal chronotropic response (from 88 +/- 28% change in sinus cycle length (normothermia) to 50 +/- 26% (hyperthermia)). These changes were also reversible with the re-establishment of normothermia. This demonstrates that clinically relevant, environmentally-induced changes in body temperature can directly and reversibly modify parasympathetic efferent responses.

Animals