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Biomedical subjects

J Stephens

Publications and source records attributed to J Stephens.

At least 19 recordsLinked to original sources
PubMed2006

Impurity band conduction in a high temperature ferromagnetic semiconductor.

The band structure of a prototypical dilute magnetic semiconductor (DMS), Ga1-xMnxAs, is studied across the phase diagram via infrared and optical spectroscopy. We prove that the Fermi energy (EF) resides in a Mn-induced impurity band (IB). Specifically the changes in the frequency dependent optical conductivity [sigma1(omega)] with carrier density are only consistent with EF lying in an IB. Furthermore, the large effective mass (m*) of the carriers inferred from our analysis of sigma1(omega) supports this conclusion. Our findings demonstrate that the metal to insulator transition in this DMS is qualitatively different from other III-V semiconductors doped with nonmagnetic impurities. We also provide insights into the anomalous transport properties of Ga1-xMnxAs.

Journal Article↗
PubMed2006

Cost effectiveness of bisphosphonates in the management of breast cancer patients with bone metastases.

BACKGROUND: Bisphosphonates are recommended to prevent skeletal related events (SREs) in patients with breast cancer and bone metastases (BCBM). However, their clinical and economic profiles vary from one agent to the other. MATERIALS AND METHODS: Using modeling techniques, we simulated from the perspective of the UK's National Health Service (NHS) the cost and quality adjusted survival (QALY) associated with five commonly-used bisphosphonates or no therapy in this patient population. The simulation followed patients into several health states (i.e. alive or dead, experiencing an SRE or no SRE, and receiving first or second line therapy). Drugs costs, infusion costs, SREs costs, and utility values were estimated from published sources. Utilities were applied to time with and without SREs to capture the impact on quality of life. RESULTS: Compared to no therapy, all bisphosphonates are either cost saving or highly cost-effective (with a cost per QALY < or = 6126 pounds sterlings). Within this evaluation, zoledronic acid was more effective and less expensive than all other options. CONCLUSIONS: Based on our model, the use of bisphosphonates in breast cancer patients with bone metastases should lead to improved patient outcomes and cost savings to the NHS and possibly other similar entities.

Bone Diseases↗
PubMed2006

Centralisation of oesophagogastric cancer services: can specialist units deliver?

INTRODUCTION: Oesophagogastric cancer surgery is increasingly being performed in only centralised units. The aim of the study was to examine surgical outcomes and service delivery within a specialist unit. PATIENTS AND METHODS: The case notes of all patients undergoing attempted oesophagogastrectomy between January 2000 and May 2003 were identified from a prospective consultant database. RESULTS: A total of 187 patients (median age, 63 years; range, 29-83 years; M:F ratio, 3.9:1) underwent attempted oesophago-gastrectomy. Of these, 91% were seen within 2 weeks of referral and treatment was instituted after a mean of 31 days (range, 1-109 days). More patients underwent surgery (63%) than neoadjuvant therapy (56%) within 1 month of referral. The main indication for surgery was invasive malignancy in 166 patients (89%). The 30-day mortality was 0.5% (1 death) and in-hospital mortality was 1.1% (2 deaths). The median length of hospital stay was 14 days (range, 7-69 days). Significant postoperative morbidity included: pulmonary complications (36%), cardiovascular complications (16%), wound infection (13%) and clinically significant anastomotic leaks (7%). Of the study group, 28 patients (15%) were admitted to ICU with a median stay of 10 days (range, 1-44 days); this accounted for 0.9% of ICU bed availability. Twelve patients (6.4%) were returned to theatre, most commonly for bleeding. The 1-year survival rates were 78%. During 2002-2003, national waiting list targets for both hernia repair and cholecystectomy were achieved. CONCLUSIONS: Despite recent increases in workload, high volume specialist units can deliver an efficient and timely service with both good treatment outcomes and minimal impact upon elective surgical waiting lists and ICU provision.

Adult↗
PubMed2005

Colloidal particles coated and stabilized by DNA-wrapped carbon nanotubes.

Single-walled carbon nanotubes (SWNTs) are dispersed in water via wrapping with short segments of single-stranded DNA (ssDNA). Small angle neutron scattering suggests a power-law exponent that is consistent with clustered nanotubes and hence marginal stability. The SWNT-ssDNA complex is used to stabilize dispersions of hydrophilic colloidal particles with the nanotubes adhered to the surface of the colloids. Near-infrared fluorescence microscopy demonstrates the interfacial band-gap fluorescence of these SWNT-coated particles, suggesting potential routes to novel platforms and applications.

Colloids↗
PubMed2005

Observation of spin Coulomb drag in a two-dimensional electron gas.

An electron propagating through a solid carries spin angular momentum in addition to its mass and charge. Of late there has been considerable interest in developing electronic devices based on the transport of spin that offer potential advantages in dissipation, size and speed over charge-based devices. However, these advantages bring with them additional complexity. Because each electron carries a single, fixed value (- e) of charge, the electrical current carried by a gas of electrons is simply proportional to its total momentum. A fundamental consequence is that the charge current is not affected by interactions that conserve total momentum, notably collisions among the electrons themselves. In contrast, the electron's spin along a given spatial direction can take on two values, +/- [planck]/2 (conventionally upward arrow, downward arrow), so that the spin current and momentum need not be proportional. Although the transport of spin polarization is not protected by momentum conservation, it has been widely assumed that, like the charge current, spin current is unaffected by electron-electron (e-e) interactions. Here we demonstrate experimentally not only that this assumption is invalid, but also that over a broad range of temperature and electron density, the flow of spin polarization in a two-dimensional gas of electrons is controlled by the rate of e-e collisions.

Journal Article↗
PubMed2004

Spin accumulation in forward-biased MnAs/GaAs Schottky diodes.

We describe a new means for all-electrical generation of spin polarization in semiconductors. In contrast with spin injection of electrons by tunneling through a reverse-biased Schottky barrier, we observe accumulation at the metal-semiconductor interface of forward-biased ferromagnetic Schottky diodes, which is consistent with a theory of spin-dependent reflection off the interface. Spatiotemporal Kerr microscopy is used to image the electron spin and the resulting dynamic nuclear polarization that arises from the nonequilibrium carrier polarization.

Journal Article↗
PubMed2004

Open vs. closed lateral internal sphincterotomy for idiopathic fissure-in-ano: a prospective, randomized, controlled trial.

PURPOSE: Internal sphincterotomy remains the "gold standard" for treatment of anal fissure but is associated with a risk of imperfect continence. Recent studies have suggested that surgical technique (open vs. closed) may influence incontinence rates after sphincterotomy. This study was designed to assess the short-term and long-term incidence of incontinence after open and closed internal sphincterotomy. METHODS: Seventy-nine patients were randomly assigned to open or closed internal sphincterotomy, performed in standardized fashion by trainee staff. Standardized questionnaires assessing continence (modified Wexner score) were administered preoperatively and at 1, 6, and 52 weeks. Postoperative stay, pain scores, complications, and fissure healing were prospectively assessed by an independent observer. RESULTS: Three patients were lost to follow-up, leaving 36 closed (16 males; mean age, 45.1 years) and 40 open (21 males; mean age, 47.9 years) internal sphincterotomy patients for assessment. All operations were performed as day case procedures with no readmissions. At six weeks postoperative, 96 percent of fissures had healed. There were no significant differences in pain scores between closed and open internal sphincterotomy at Day 1 or Day 3 postoperative. New incontinence of any grade was seen in 6.8 percent of patients at 52-week follow-up. Three patients (4.1 percent, 1 closed, 2 open) suffered major incontinence at 52 weeks. There were no significant differences in continence at 1, 6, or 52 weeks, although more open patients experienced minor imperfections at 1 week. CONCLUSIONS: Incontinence after internal sphincterotomy is not insignificant. The technique (closed vs. open) does not seem to influence incontinence rates.

Adult↗
PubMed2004

Parastomal hernia repair.

OBJECTIVE: The aim of this study was to audit the results of parastomal hernia repair. METHODS: A retrospective review was made of all patients having parastomal hernia repair at 2 teaching hospitals over a 12-year period. RESULTS: Forty-three patients had 51 parastomal hernia repairs. Three types of hernia repair were used: 14 (28%) local suture, 19 (37%) local mesh repair and 18 (35%) stoma relocation. Three patients died and significant complications occurred in 65% of repairs. Parastomal hernia recurred in 18 (38%) of repairs. This was greatest with a sutured repair (59%) and least in patients having stoma relocation (24%). Repair with mesh was associated with a 39% recurrence rate. No significant statistical difference was found for the results of these repairs. CONCLUSION: Parastomal hernia repair is associated with high rates of morbidity, mortality and recurrence. Repair should not be undertaken without a good indication.

Adult↗
PubMed2003

The burden of acute postoperative pain and the potential role of the COX-2-specific inhibitors.

Pain has been recognized as a problem of global proportions, and postoperative pain is one of the most common types of pain. Postoperative pain is acute and, although it is preventable and/or treatable, it is often undertreated. Lack of appropriate analgesic management has significant impact on clinical and economic outcomes. Negative clinical outcomes of inadequately managed acute postoperative pain include extended hospitalization, compromised prognosis, higher morbidity and mortality, and the development of a chronic pain state as a result of neuronal plasticity. Although estimating the economic burden of postoperative pain is difficult, this burden is considerable and results from direct costs due to excess health-care resource use, as well as indirect costs due to reduced patient functionality and productivity. These latter factors also have a significant adverse impact on patients' quality of life and may be associated with the development of depression and anxiety. Thus, improved clinical outcomes are dependent not only on the availability of effective drugs but also on their appropriate utilization. A multimodal approach incorporating different drugs and techniques is effective in reducing postoperative pain but is limited by the currently available therapies. The efficacy of opioids is well established, but there are concerns about dependency, respiratory depression and side-effects, which patients often find intolerable. Non-steroidal anti-inflammatory drugs (NSAIDs) are effective as adjunctive medication in a multimodal regimen but are associated with side-effects, such as platelet dysfunction and renal and gastrointestinal toxicity, that have special clinical significance in patients undergoing surgical procedures. Cyclooxygenase-2-specific inhibitors such as celecoxib, rofecoxib and valdecoxib, were developed to provide the efficacy of non-specific NSAIDs while limiting associated toxicity. These agents have demonstrated analgesic efficacy and an opioid-sparing effect in a variety of surgical procedures, suggesting their value as an alternative to non-specific NSAIDs. Further studies are needed to determine the impact of these drugs on clinical and economic outcomes when used in a programme of postsurgical pain management.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

Prosthetic valve endocarditis: early and late outcome following medical or surgical treatment.

OBJECTIVE: To compare the early and late outcome of medical and surgical treatment in patients with prosthetic valve endocarditis within a single unit. DESIGN: All patients with proven prosthetic valve endocarditis treated in one institution between 1989 and 1999 were studied. RESULTS: There were 66 patients (24 female, 42 male), mean (SD) age 57 (14) years. Of these, 28 were treated with antibiotics alone and 38 with a combination of antibiotics and surgery. The in-hospital mortality for the antibiotic group was 46% and for the surgical group, 24%. However, seven patients in the antibiotic group were considered too sick for curative treatment. The mortality in the remaining 21 medically treated patients (6/21; 29%) was not significantly different from that in the surgically treated patients (p = 0.15). Six patients in the medically treated group and one in the surgically treated group required late reoperation. Endocarditis recurred in three patients in the medically treated group, two of whom were treated surgically, and in one patient in the surgically treated group. Kaplan-Meier survival at 10 years was 28% in the medically treated group v 58% in the surgically treated group (p = 0.04). Freedom from endocarditis at five years was 60% in the surgically treated group and 65% in the medically treated group. CONCLUSIONS: Prosthetic valve endocarditis is a serious condition with high early and late mortality, irrespective of the treatment employed. These data show that selected patients with prosthetic valve endocarditis can be successfully treated with antibiotics alone. If required, surgery in this difficult group of patients can provide satisfactory freedom from recurrent infection.

Anti-Bacterial Agents↗
PubMed2002

Colorectal cancer in patients with chronic renal failure: the effect of dialysis or renal transplantation.

OBJECTIVE: This study reports the characteristics and surgical outcome of colorectal cancer in patients with chronic renal failure treated either by renal transplantation or dialysis. METHODS: Two thousand four hundred and seventeen patients with CRF (1387 transplant and 1030 dialysis) were treated at The Queen Elizabeth Hospital, South Australia, between January 1967 and September 2000. RESULTS: Fourteen have developed colorectal cancer and had their clinical records reviewed. Nine patients were renal transplant recipients and 5 patients were treated with dialysis. Eight patients had surgery. Chemotherapy was given palliatively to 3 patients. One patient died in hospital postoperatively. Seven patients with a renal transplant had notes available. Six presented with late stage disease and all were dead within 9 months of presentation from their disease. In the dialysis patients, tumour stage at presentation was not so advanced and although all the patients have died, the cause of death was secondary to the colorectal cancer in only 2 patients. CONCLUSIONS: This study highlights the poor outcome of patients who have had renal transplant and develop colorectal cancer. Immunosuppression and late diagnosis are implicated in this poor outcome.

Journal Article↗
PubMed2001

CV706, a prostate cancer-specific adenovirus variant, in combination with radiotherapy produces synergistic antitumor efficacy without increasing toxicity.

Radiation is an effective means of treating localized prostate cancer. However, up to 40% of men with certain risk factors will develop biochemical failure 5 years after radiotherapy. CV706, a prostate cell-specific adenovirus variant, is currently in clinical trials for the treatment of recurrent organ-confined prostate cancer. We demonstrated previously that a single administration of CV706 at 5 x 10(8) particles/mm3 of tumor eliminated established tumors within 6 weeks in nude mouse xenografts (Rodriguez et al., Cancer Res. 57: 2559-2563, 1997). We now demonstrate that CV706-mediated cytotoxicity is synergistic with radiation. In vitro, addition of radiation to CV706 resulted in a synergistic increase of cytotoxicity toward the human prostate cancer cell line LNCaP and a significant increase of virus burst size, with no reduction in specificity of CV706-based cytopathogenicity for prostate cancer cells. In vivo, prostate-specific antigen (+) LNCaP xenografts of human prostate cancer were treated with CV706 (1 x 10(7) particles/mm3 of tumor), 10 Gy of single fraction local tumor radiation, or both. Tumor volumes of the group treated with CV706 or radiation was 97% or 120% of baseline 6 weeks after treatment. However, when the same dose of CV706 was followed 24 h later with the same dose of radiation, the tumor volume dropped to 4% of baseline at this time point and produced antitumor activity that was 6.7-fold greater than a predicted additive effect of CV706 and radiation. Histological analyses of tumors revealed that, compared with CV706 or radiation alone, combination treatment with two agents increased necrosis by 180% and 690%, apoptosis by 330% and 880%, and decreased blood vessel number by 1290% and 600%, respectively. Importantly, no increase in toxicity was observed after combined treatment when compared with CV706 or radiation alone. These data demonstrate that CV706 enhances the in vivo radioresponse of prostate tumors and support the clinical development of CV706 as a neoadjuvant agent with radiation for localized prostate cancer.

Adenoviridae↗
PubMed2001

Cell culture conditions affect LPS inducibility of the inflammatory mediators in J774A.1 murine macrophages.

Peripheral blood monocytes and tissue macrophages contribute significantly to the inflammatory response. Bacterial lipopolysaccharide (LPS) has profound effects on these cells including, but not limited, to differentiation into macrophages, production of reactive nitrogen and oxygen species and secretion of pro-inflammatory cytokines. Herein, we describe a variant of the J774A.1 murine macrophage line that is reversibly resistant to multiple effects of LPS when cultured in different types of media. J774A.1 cells are adherent and spread out when cultured in DMEM/F12; however, when cultured in RPMI 1640, the cells are rounded and relatively non-adherent. Different types of tissue culture plates, sera, and media supplements were not responsible for these changes. We examined LPS-induced reactive nitrogen species using the Greiss reagent. J774A.1 cells cultured in RPMI exhibit a 5-fold increase in nitrites in culture supernatants after LPS stimulation whereas those in DMEM/F12 do not. Zinc staining of total cellular protein of cells in COHLY ET AL. RPMI and DMEM/F12 electrophoresed on a SDS-PAGE showed noticeable banding differences. LPS-induced cytokine gene expression was studied by RT-PCR. LPS induced TNF-alpha, IL-1alpha, IL-1beta, and sIL-1Ra in cells cultured in RPMI but not those cultured in DMEM/F12 with the exception of TNFalpha. This report shows that environmental factors contained in the culture medium alone can reversibly alter the biochemical nature of monocytes and macrophages.

Animals↗
PubMed2000

Hepatocyte transplantation in acute liver failure.

The majority of patients with acute liver failure (ALF) die waiting for orthotopic liver transplantation (OLT). No other treatment modality is shown to improve survival. This study was conducted to assess the safety and feasibility of hepatocyte transplantation (HT) and subsequent engraftment and function of donor cells. Functional and structural integrity of cryopreserved and thawed human hepatocytes were assessed by their morphological characteristics, induction of P-4501A1 transcription, and survival in vivo by xenotransplantation into rats. Five patients with severe ALF underwent intrasplenic (4 patients) and/or intrahepatic (2 patients) HT through angiography under cyclosporine immunosuppression. All patients had grade III to IV encephalopathy and factor V levels less than 0.5 U/mL, were ventilator and dialysis dependent, and were not OLT candidates. Three of the 5 patients who survived 48 hours after HT had substantial improvement in encephalopathy scores, arterial ammonia levels, and prothrombin times. Clinical improvement was paralleled by an increase in aminopyrine and caffeine clearances. All 3 patients lived substantially longer than expected based on clinical experience after HT (12, 28, and 52 days) but eventually died. Postmortem examination showed the presence of transplanted hepatocytes in liver and spleen by light microscopy and fluorescent in situ hybridization (FISH). Cryopreserved and thawed human hepatocytes can be transplanted into recipients with ALF with some acceptable but definite complications. Engraftment of donor hepatocytes was proven by histological examination and FISH by both transjugular biopsy and at autopsy. Improvement in brain edema, encephalopathy grade, and clearance of antipyrine and caffeine suggested function, albeit with a 24- to 72-hour delay posttransplantation.

Adult↗
PubMed1999

Azithromycin compared with penicillin G benzathine for treatment of incubating syphilis.

BACKGROUND: Preventive therapy is an important element of syphilis control efforts. No currently recommended, single-dose alternatives to penicillin G benzathine are available for treatment of incubating syphilis. OBJECTIVE: To evaluate the use of a single 1.0-g dose of azithromycin for treatment of persons recently exposed to sexual partners with infectious syphilis. DESIGN: Single-center, open-label, randomized pilot study to compare azithromycin with penicillin G benzathine therapy. Participants were evaluated serologically for 3 months. SETTING: Sexually transmitted disease clinic in Birmingham, Alabama. PARTICIPANTS: 96 participants who in the preceding 30 days had been exposed to partners with infectious syphilis through sexual intercourse. MEASUREMENTS: Syphilis prevention, as indicated by nonreactive serologic tests (rapid plasma reagin and fluorescent treponemal antibody-absorbed), throughout the 3-month follow-up. RESULTS: Among 96 participants enrolled, none of 40 evaluable persons in the azithromycin group and none of 23 evaluable persons in the penicillin group developed evidence of syphilis. Significantly more penicillin-treated participants (21 of 44 [48%]) than azithromycin-treated participants (12 of 52 [23%]) became nonevaluable during follow-up (P = 0.01). CONCLUSION: A single 1.0-g dose of azithromycin seems to be efficacious for prevention of syphilis in persons exposed to infected sexual partners.

Administration, Oral↗
PubMed1999

Liver and bile duct pathology following Cryptosporidium parvum infection of immunodeficient mice.

Patients with acquired immune deficiency syndrome (AIDS) and boys with mutations of the CD154 gene (causing congenital X-linked immunodeficiency with hyper-IgM [XHIM]) are susceptible to chronic infections of the biliary tract with Cryptosporidium parvum (CP) that may lead to biliary sclerosis and ultimately to cholangiocarcinoma. To determine whether the CP infection and the consequent immune response contribute independently to this morbidity, we infected mice with severe combined immunodeficiency (SCID) or with disrupted genes for CD154, CD40, or interferon gamma (IFN-gamma) with CP. Even when CP infection persisted for 16 weeks, the SCID mice developed only mild triaditis, without apoptosis of biliary epithelial cells (BEC). Fifty percent of the CD154 knockout mice developed lobular hepatitis with acute and chronic triaditis. The CD40 knockout mice developed marked triaditis, and the IFN-gamma knockouts either succumbed to enteritis or survived to develop marked triaditis, portal fibrosis, biliary sclerosis, necrosis with dilation of duct-like structures within the porta hepatis, and dysplastic changes. CP-infected SCID mice reconstituted with T cells from IFN-gamma knockout donors either developed severe enteritis or survived to develop triaditis, cholangitis, lobular hepatitis with periductular sclerosis, and scarring. Mice with disruptions of both the CD40 and IFN-gamma genes remained infected by CP and developed bile duct and liver disease, but not enteritis. Our results suggest that T-cell cytokines are required for the inflammatory and sclerosing responses to CP infection in immunodeficient animals. The response of immunodeficient mice to CP infection may model at least the initial steps toward the development of sclerosing cholangitis or bile duct cancers in XHIM patients.

Animals↗