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Biomedical subjects

S Long

Publications and source records attributed to S Long.

At least 37 records · Page 2Linked to original sources
PubMed2000

Vacuum disk and facet phenomenon in a dog with cauda equina syndrome.

A 7-year-old castrated male Rottweiler was evaluated for an 18-month history of bilateral hind limb lameness, signs of pain on rising, and mild ataxia. A gas-filled lumbosacral disk space (vacuum disk phenomenon) was revealed by use of computed tomography. Additional smaller gas bubbles were in the periphery of the disk and between the degenerated L5-L6 dorsal articular facets (vacuum facet phenomenon). Vacuum disk and facet phenomena have been described in humans with degenerative disk and vertebral articular facet joint disease; gas attracted from surrounding tissues accumulates within clefts of the degenerated disk or in unstable facet joints. Vacuum disk phenomenon has been reported in dogs and indicates degenerative disk disease. The phenomenon is more commonly observed by use of computed tomography, compared with conventional radiography, and can be elicited by hyperextension of the vertebral column.

Animals↗
PubMed2000

Characterization of the "helix clamp" motif of HIV-1 reverse transcriptase using MALDI-TOF MS and surface plasmon resonance.

A helix-turn-helix motif in the crystal structure of human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) was proposed to be a conserved nucleic acid binding domain among several nucleotide polymerizing enzymes (Hermann, T.; Meier, T.; Götte, M.; Heumann, H. Nucleic Acids Res. 1994, 22, 4625-4633). The sequence of this domain is homologous to 259KLVGKL-(X)16KLLR284 of HIV-1 RT, which acts as a "helix clamp" grasping the template-primer (T-P) complex. We characterized the helix clamp motif using MALDI-TOF MS and surface plasmon resonance (BIAcore). Our studies showed that the "helix clamp" has a nucleic acid binding function that may not be sequence specific. This evidence suggests that ionic interactions between the helix clamp and oligonucleotide backbone are not solely responsible for binding. Secondary and tertiary structures of the protein may also play a significant role in nucleic acid binding. The association and dissociation constants, ka and kd, for the binding of single-stranded oligonucleotide to the helix clamp were determined to be 7.03 x 10(3) M(-1) s(-1) and 1.22 x 10(3) s(-1), respectively.

Amino Acid Sequence↗
PubMed2000

Allogeneic blood and bone-marrow stem-cell transplantation in haematological malignant diseases: a randomised trial.

BACKGROUND: Autologous transplantation with peripheral blood stem cells (PBSC) results in faster haematopoietic-cell repopulation than with bone marrow. We prospectively compared bone marrow and PBSC for allogeneic transplantation. METHODS: Adult HLA-identical sibling donors provided bone marrow and lenograstim-mobilised PBSC. 39 patients with malignant haematological disorders were infused with either bone marrow (n=19) or PBSC (n=20) after standard conditioning regimens in a double-blind, randomised fashion. The identity of the infused products for all patients remained masked until 1 year after the last patient had received transplantation. FINDINGS: The PBSC group had significantly faster neutrophil recovery to 0.5x10(9)/L (median 17.5 vs 23 days, p=0.002), and platelet recovery to 20x10(9)/L (median 11 vs 18 days, p<0.0001) and to 50x10(9)/L (median 20.5 vs 27 days, p=0.02) than the bone-marrow group. PBSC patients were discharged from hospital earlier than were bone-marrow patients (median 26 vs 31 days, p=0.01). At 4 weeks after transplantation, absolute lymphocytes (0.48 vs 0.63, p=0.08) and CD25 cells (0.04 vs 0.08, p=0.007) were higher in the PBSC group, and the proportion of patients with absolute lymphopenia (74% vs 33%, p=0.03) and CD4 lymphopenia (59% vs 24%, p=0.05) was significantly higher in the bone-marrow group. There was no significant difference in the occurrence of acute or chronic graft-versus-host disease and overall survival. The probability of relapse was significantly higher in the bone-marrow group than in the PBSC group (p=0.01); all five relapses occurred among bone-marrow recipients. INTERPRETATION: Our small study indicates that PBSCs are better than bone marrow for allogeneic transplantation from HLA-identical siblings in terms of faster haematopoietic and immune recovery, and have the potential to reduce disease recurrence.

Adult↗
PubMed2000

Archaeal promoter-directed expression of the Halobacterium salinarum catalase-peroxidase gene.

The Halobacterium salinarum catalase-peroxidase gene was subcloned into shuttle vectors pWL102 and pWL202 and expressed under the control of different archaeal promoters. When Hbt. salinarum was transformed with the catalase-peroxidase gene under the control of its own promoter, catalase-peroxidase activity increased twofold. Catalase-peroxidase activity increased threefold when Hbt. salinarum was transformed with the catalase-peroxidase gene under the control of a tRNA promoter. This bifunctional enzyme in Hbt. salinarum was not induced by environmental stresses such as H2O2, intense light, darkness, high temperature, low temperature, redox inhibitors, heavy metals, or ions.

Base Sequence↗
PubMed2000

Comparison of marrow and blood cell yields from the same donors in a double-blind, randomized study of allogeneic marrow vs blood stem cell transplantation.

Forty healthy adult donors underwent marrow (BM) as well as peripheral blood (PBSC) stem cell collections for their HLA-identical adult siblings with hematologic malignancies. BM was harvested on day 1 (target 3 x 108 nucleated cells/kg, 10 microg/kg lenograstim (glycosylated G-CSF) administered on days 2-6, and a single leukapheresis performed on day 6. The blood volume processed was the higher of 200% donor blood volume or 10 liters. The total nucleated cell (TNC) yields from PBSC were 1.1- to 4.3-fold higher than BM (median 7.0 vs 3.1 x 10(8)/kg, P < 0.0001). Although BM contained a higher proportion of CD34+cells (1.3% vs 0.7%, P < 0. 0001) and a comparable proportion of CD3+ cells (median 29% vs 26%, P = 0.4), the absolute numbers of CD34+ and CD3+ cells and their subsets were several times higher in PBSC. There was a poor correlation between BM and PBSC CD34 and TNC numbers, but a significant correlation between BM and PBSC CD3 numbers. Only five of 40 BM harvests contained >/=2 x 10(6) CD34+ cells/kg compared with 35 of 40 PBSC harvests (P < 0.0001). We conclude that the numbers of progenitor and immunocompetent cells in PBSC are several times higher than in BM. It is possible to collect adequate numbers of progenitor cells from blood after lenograstim stimulation more frequently than from marrow, and donors yielding low quantities of progenitor cells from BM usually deliver better quantities from PBSC. Bone Marrow Transplantation (2000) 25, 501-505.

Adjuvants, Immunologic↗
PubMed2000

A low CD34+ cell dose results in higher mortality and poorer survival after blood or marrow stem cell transplantation from HLA-identical siblings: should 2 x 10(6) CD34+ cells/kg be considered the minimum threshold?

We studied the effect of the CD34+ cell dose on transplant-related mortality (TRM) and survival in 39 patients randomized to receive lenograstim-mobilized PBSCT (n = 20) or BMT (n = 19) from HLA-identical siblings. Both marrow and blood were harvested, and one infused in a double-blind fashion. The median nucleated (7.0 vs 3.2 x 10(8)/kg; P < 0.0001), CD34+ (3.7 vs 1.5 x 10(6)/kg; P = 0.002), CFU-GM (42 vs 19 x 10(4)/kg; P = 0.002), and CD3+ (1.9 vs 0.3 x 10(8)/kg; P < 0.0001) cell doses with PBSCT were higher. Thirteen patients (6 BMT and 7 PBSCT) experienced TRM at 15-733 days (median 57); 10 of 20 receiving <2 x 10(6) CD34+ cells/kg compared with three of 19 receiving > or =2. Eight of 20 patients receiving <2 x 10(6) CD34+ cells/kg are alive compared with 14 of 19 receiving > or =2. In Cox analysis, CD34+ cell dose > or =2 x 10(6)/kg was associated with lower TRM (RR 0.2, P = 0.01), and higher overall (RR 3.7, P = 0.01) and event-free (RR 3.2, P = 0.02) survival. Other cell populations and the source of stem cells did not affect TRM or survival. We conclude that 2 x 10(6) CD34+ cells/kg may be the ideal minimum cell dose for allogeneic transplantation although lower doses do not preclude successful therapy. Since the likelihood of obtaining this threshold CD34+ cell number is significantly greater from blood than marrow, PBSCT may be preferable to marrow for allografts from HLA-identical siblings.

Adolescent↗
PubMed2000

Scale-up of an oil/water cream containing 40% diethylene glycol monoethyl ether.

The purpose of this study was to scale up an oil/water (o/w) cream formulation containing 40% diethylene glycol monoethyl ether (DGME), developed via 300-g laboratory batches in a 2(5-2) fractional factorial design, to 7-kg batch sizes in a Brogli-10 homogenizer. The o/w cream was manufactured via a standard phase-inversion process in the Brogli-10 homogenizer. Partitioning studies of DGME were conducted in test tubes at ambient temperature and after 24 hr at 70 degrees C in a convection oven. Phase height was measured by vernier calipers. Microscopy studies of excipients with and without treatment with water or a DGME/water mixture were conducted with a Nikon microscope after equilibration at 35 degrees C for 24 hr. During creation of the 7-kg pilot-scale batches, congealed material was observed between the sweep agitation blade and the discharge port, where the Brogli-10 homogenizer is not temperature jacketed. Factors that increased the amount of congealed material were higher temperatures during primary emulsification and longer cooling times. Partitioning studies revealed that DGME resides in the aqueous external phase of this formulation. Microscopy studies revealed that DGME in the external phase of this cream has a profound impact on the solubility of certain solid, waxy excipients (e.g., cetyl alcohol and polyoxyethylene-2-stearyl ether) at 35 degrees C. From this study, it appears that DGME resides in the external phase of the o/w cream. During manufacturing, it is hypothesized that the presence of DGME in the external phase alters the solubility of certain solid, waxy excipients in the formula such that they no longer primarily reside in the internal oil phase. On cooling, these materials precipitate or congeal in the external phase. The fractional factorial experimental design at the 300-g laboratory scale did not predict the issues encountered during scale-up. Differences between laboratory scale and pilot plant scale that explain why this phenomenon was not seen during laboratory scale are differences in cooling times, nonjacketed or "cold spots" in the Brogli-10 homogenizer, and a low proportion of congealed material in relation to the total batch size (< 1.5%).

Chemical Phenomena↗
PubMed2000

A comparative evaluation of Humphrey perimetry and the multi-channel pattern visual evoked potentials.

PURPOSES: To compare the multi-channel pattern visual evoked potentials to Humphrey perimetry in the assessment of central visual function in primary open angle glaucoma. METHODS: The multi-channel checkerboard reversal PVEPs waves to full-field and half-field stimulus of 25 normal persons and 74 patients with primary open angle glaucoma were recorded and analyzed, All patients were examined using Humphrey Field Analyzer. The area of visual field corresponding to the area of retina stimulated during multi-channel PVEPs testing were analysed, straight-line correlation and regression analyses of the various multi-channel PVEPs parameters and the total dB losses were performed. RESULTS: The multi-channel PVEPs demonstrated a low detection rate compared with Humphrey perimetry in the early glaucoma, absolute latency and field loss were correlated in the late stage of glaucoma, and absolute amplitude and field loss were not correlated. CONCLUSIONS: In relation to signalling "early" loss the multi-channel PVEPs was inferior to Humphrey perimetry, in late loss of primary open angle glaucoma, multi-channel PVEPs can provide a valuable, objective complement to Humphrey perimetry.

Adolescent↗
PubMed1999

Vitamin E-TPGS increases absorption flux of an HIV protease inhibitor by enhancing its solubility and permeability.

PURPOSE: To investigate the effect of vitamin E-TPGS, d-alpha-tocopheryl polyethylene glycol 1000 succinate, on the solubility and permeability of amprenavir, a potent HIV protease inhibitor. METHODS: The aqueous solubility of amprenavir was measured as a function of vitamin E-TPGS concentration. Directional transport through Caco-2 cell monolayers was determined in the presence and absence of vitamin E-TPGS and P-glycoprotein inhibitors. Absorption flux was estimated from Caco-2 cell permeability and aqueous solubility. RESULTS: The solubility of amprenavir in a pH 7 buffer at 37 degrees C was 0.036+/-0.007 mg/mL. The solubility linearly increased with increasing vitamin E-TPGS concentration (above 0.2 mg/mL). Polarized transport was demonstrated in the basolateral to apical direction, exceeding apical to basolateral transport by a factor of 6. The active efflux system was inhibited by vitamin E-TPGS and known P-glycoprotein inhibitors verapamil and GF120918. CONCLUSIONS: The solubility of amprenavir was improved in the presence of vitamin E-TPGS through micelle solubilization. Vitamin E-TPGS inhibits the efflux system and enhances the permeability of amprenavir. Overall, vitamin E-TPGS enhanced the absorption flux of amprenavir by increasing its solubility and permeability. The enhancement is essential to the development of the novel soft gelatin capsule formulation of amprenavir for use in the clinic.

Algorithms↗
PubMed1999

Intratumoral delivery of IL-12 gene by polyvinyl polymeric vector system to murine renal and colon carcinoma results in potent antitumor immunity.

We have utilized a nonviral, polymeric interactive non-condensing (PINC) gene delivery system to deliver IL-12 to two different types of murine tumors, an immunogenic renal cell carcinoma, Renca, and a non-immunogenic colon cell carcinoma, CT26. The delivery of IL-12/polyvinyl pyrrolidone (PVP) complexes into Renca led to the expression of IL-12 (146 +/- 89 pg/mg) and IFN-gamma (160 +/- 82 pg/mg) from explanted tumors in culture supernatants. Treated tumors showed increased infiltration of NK, CD4+ and CD8+ T cells and up-regulation of MHC class I molecules on leukocytes in both tumors and lymph nodes. Fifty per cent of tumor-bearing mice rejected Renca or CT26 tumors following IL-12/PVP treatments given at optimal doses of 24 and 48 micrograms, respectively. While polymorphonuclear cells (PMNs) were partially involved in the development of the antitumor immune response elicited by IL-12/PVP treatment, CD8+ T cells were found to be the primary effectors. In contrast, CD4+ T cells did not appear to play a significant role in the development of tumor specific immunity. Finally, mice that rejected the tumors following IL-12/PVP treatment were protected against a second challenge with the same tumor. These data provide evidence that a nonviral IL-12 gene delivery system is well tolerated and generates a potent immune response against established tumors.

Animals↗
PubMed1999

The pharmacist's role in primary care within an integrated health system.

I read, with interest, the paper by Rosser and Kasperski. I was struck by how similar and applicable the problems and issues identified for family physicians are to those pharmacists face today in Canada's health system. There is a need for a coordinated and systematic approach to address infrastructure support for all primary-care providers. In this companion article, I will provide evidence to support the Ontario College of Family Physicians' position on strengthening family physicians' abilities to provide excellent primary care. In addition, I will make a case for support of greater involvement of pharmacists in community-based primary-care teams.

Canada↗
PubMed1998

Comorbidity and age as predictors of risk for early mortality of male and female colon carcinoma patients: a population-based study.

BACKGROUND: Colon carcinoma primarily affects persons 65 years and older. Seventy-five percent of the incident tumors affect persons in this age group. Because of their advanced age, older patients already may be coping with other concomitant major physical illnesses. This article documents preexisting diseases in older colon carcinoma patients at diagnosis and evaluates the effects of their comorbidity burden on early mortality. METHODS: Prevalence of comorbid conditions was assessed by a retrospective medical records review of an age-stratified random sample of male and female patients aged 55-64 years, 65-74 years, and 75+ years (males, n=799; females, n=811). Data were collected on comorbidity by the National Institute on Aging (NIA) and National Cancer Institute (NCI) and merged with NCI Surveillance, Epidemiology, and End Results (SEER) tumor registry data. RESULTS: Hypertension, high impact heart conditions, gastrointestinal problems, arthritis, and chronic obstructive pulmonary disease emerged as the most prominent comorbid conditions in the NIA/NCI SEER Study sample. The prevalence of comorbidity in the number and type of conditions was similar for both men and women (e.g., 40% of each gender had > or = 5 comorbidities). Within 2 years of diagnosis, 28% (n=454) of the patients had died. The number of comorbid conditions was significant in predicting early mortality in a model including age, gender, and disease stage (P=0.0007). Certain comorbidities, classified as "current problem," added significantly to a basic model (e.g., heart problems, alcohol abuse, liver disease, and deep vein thrombosis). CONCLUSIONS: Although disease stage at time of diagnosis of colon carcinoma is a crucial determinant of patient outcome, comorbidity increases the complexity of cancer management and affects survival duration. Cancer control and treatment research questions should address comorbidity issues pertinent to the age group primarily afflicted with colon carcinoma (i.e., the elderly).

Age Factors↗
PubMed1998

A suicide disguised as a homicide: return to Thor Bridge.

Suicides staged as homicides are uncommon. We present a case of a self-inflicted gunshot wound of the chest disguised by the victim as a homicide, using a method described by Sir Arthur Conan Doyle in his Sherlock Holmes story, "The Problem of Thor Bridge."

Cause of Death↗
PubMed1998

Analysis of peak magnitude and duration of analgesia produced by local anesthetics injected into sympathetic ganglia of complex regional pain syndrome patients.

OBJECTIVE: Pain-relieving effects of lidocaine/bupivicaine local anesthetic (LA) and saline (S) block of sympathetic ganglia (stellate block, 4 patients; lumbar sympathetic block, 3 patients) were compared in 7 complex regional pain syndrome (CRPS) patients on a double-blind crossover basis to evaluate the diagnostic and therapeutic value of local anesthetic sympathetic blocks. DESIGN: Patients rated their pain on a visual analog scale before and after blocks and were tested for mechanical allodynia one-half hour after blocks. Thereafter, they rated their pain intensity in diaries four times a day for 7 days. Each patient received two blocks, S and LA, and served as his own control. RESULTS: Both S and LA injections of sympathetic ganglia produced large reductions in pain intensity in 6 of 7 patients 30 minutes after block. These large reductions were accompanied by the reversal of mechanical allodynia in both S and LA. The mean difference between initial peak reduction in pain intensity produced by saline (68.7%) and active local anesthetic (74.4%) did not approach statistical significance. In striking contrast, the mean duration of pain relief was reliably longer in the case of LA (3 days, 18 hours) as compared with S ( 19.9 hours), a difference that occurred in all 7 patients. In a larger sample of 41 CRPS patients, signs of sympathetic efferent blockade, including Homer' s syndrome or skin surface temperature change, were not predictive of initial peak magnitude of pain relief from sympathetic blockade but were predictive of duration of pain reduction. CONCLUSION: The combination of these results provides evidence that duration of pain relief is affected by injection of local anesthetics into sympathetic ganglia. These results indicate that both magnitude and duration of pain reduction should be closely monitored to provide optimal efficacy in procedures that use local anesthetics to treat CRPS.

Adult↗
PubMed1998

Long-term outcome of brain manganese deposition in patients on home parenteral nutrition.

Manganese intoxication has been described in children on long term parenteral nutrition presenting with liver and nervous system disorders. Cases are reported of a brother and sister on long term parenteral nutrition with hypermanganesaemia and basal ganglia manganese deposition, detected by magnetic resonance imaging (MRI), without overt neurological signs. Following reduction of manganese intake, basal ganglia manganese was monitored by repeated MRI, and neurological and developmental examinations. An MRI intensity index of the globus pallidus declined over a three year period from 0.318 and 0.385 to 0.205 and 0.134 with concomitant falls in whole blood manganese from 323 and 516 to 226 and 209 nmol/l (normal range, 73-210 nmol/l). Unlike adult experience these children developed normally without neurological signs. In conclusion, deposited manganese is removed from neural tissue over time and the prognosis is good when neurological manifestations and liver disease are absent.

Basal Ganglia↗
PubMed1997

Expression of biologically active human insulin-like growth factor-I following intramuscular injection of a formulated plasmid in rats.

Recent evidence has shown that insulin-like growth factor-I (IGF-I) plays an important role in the development, maintenance, and regeneration of peripheral nerves and skeletal muscle. IGF-I offers the potential to treat neuromuscular diseases in humans. We have developed a nonviral gene therapy method to express and produce localized and sustained therapeutic levels of IGF-I within target muscles by intramuscular injection of formulated plasmids. The purpose of the present study was to demonstrate that intramuscular injection of a plasmid encoding human IGF-I (hIGF-I) and engineered to restrict expression to skeletal muscle produces sustained local concentrations of biologically active hIGF-I. Normal rats received a single intramuscular injection of plasmids formulated as a complex with polyvinylpyrrolidone (PVP). Results show that hIGF-I mRNA and hIGF-I protein were detectable in the injected muscles for the duration of the study (28 days), whereas the hIGF-I protein was not detected in blood. Biological activity of hIGF-I was determined by immunodetection of a nerve-specific growth-associated protein, GAP-43, an indicator of motor neuron sprouting. Placement of human growth hormone (hGH) 3' untranslated region enhanced GAP-43 staining, probably due to improved secretion of hIGF-I. Enhanced immunoreactivity of GAP-43 was observed in muscles injected with the formulated hIGF-I plasmid when compared to controls. These results demonstrate that intramuscular injection of hIGF-I plasmid formulated as a complex with PVP produces a localized and sustained level of biologically active hIGF-I.

Animals↗
PubMed1997

Counting the cost: hospital versus home central venous catheter survival.

We compared catheter survival and sepsis rates in a tertiary paediatric gastroenterology centre with those at home in the same patients. We examined whether there were differences in the safety in the two locations, and estimated the financial and opportunity cost implications of any difference. We used survival analysis to analyse differences. Surgical records were audited to determine venous access workload, and to estimate cost implications. Twenty patients with chronic intestinal failure but stable parenteral nutrition requirements, ranging from 0.04-15.83 years of age were studied. The duration of line survival and sepsis-free intervals and rates of re-operation for venous access were determined to estimate morbidity and costs. The study encompassed 28 patient-years in hospital and 48 patient-years at home. There was a significant reduction in the rate of sepsis at home compared with hospital (Z = 4.30, P < 0.00001), and a similar improvement in line survival (Z = 4.36, P < 0.00001). Line insertions accounted for 21% of minor surgery in our hospital, one third being reinsertions. We conclude that central venous catheter sepsis rates are greatly improved at home. If home results could be achieved in the hospital setting, considerable cost savings would be made.

Adolescent↗