Portable microsensors based on individual SnO2 nanowires.

Individual SnO(2) nanowires were integrated in suspended micromembrane-based bottom-up devices. Electrical contacts between the nanowires and the electrodes were achieved with the help of electron- and ion-beam-assisted direct-write nanolithography processes. The stability of these nanomaterials was evaluated as function of time and applied current, showing that stable and reliable devices were obtained. Furthermore, the possibility of modulating their temperature using the integrated microheater placed in the membrane was also demonstrated, enabling these devices to be used in gas sensing procedures. We present a methodology and general strategy for the fabrication and characterization of portable and reliable nanowire-based devices.

Dose-reduced conditioning and allogeneic hematopoietic stem cell transplantation from unrelated donors in 42 patients.

PURPOSE: A fludarabine-based "nonmyeloablative" preparative regimen was investigated in 42 patients with hematological malignancies receiving hematopoietic stem cell grafts from unrelated volunteer donors. EXPERIMENTAL DESIGN: Recipient conditioning consisted of fludarabine 30 mg/m(2) on days -6 to -2 and i.v. busulfan 3.3 mg/kg on days -6 to -5. Antithymocyte globuline was added at 2.5 mg/kg i.v. on days -5 to -2. The patients were grafted with bone marrow (n = 13) or peripheral blood stem cells either unmanipulated (n = 20) or CD34+ selected (n = 9). Graft-versus-host disease prophylaxis was performed with cyclosporine A (CsA, n = 12), CsA/methotrexate (n = 12), or CsA/mycophenolate mofetil (n = 18). RESULTS: With a median follow-up of 13 months (range, 5-26 months), the actuarial disease-free survival is 64% and 38% for patients with lymphoid malignancies and standard-risk leukemia compared with only 14% for patients with high-risk disease. The main cause of treatment failure was relapse of disease in high-risk patients (n = 14). An increased incidence of primary (n = 1) or secondary graft-failure (n = 8) was observed (21%). Chimerism analysis of CD56+/CD3--sorted natural killer (NK) cells, available in 10 patients, showed an impaired increase of donor NK cell chimerism between day 10 and 30 after transplantation in three of four patients with graft failure, whereas the percentage of donor NK cells surpassed 75% in all of the six patients with stable engraftment. CONCLUSIONS: Unrelated transplants after dose-reduced conditioning are associated with a higher risk of graft-failure. Pretransplant host immunosuppression has to be optimized to overcome resistance to grafts from unrelated donors after nonmyeloablative conditioning therapy.

Pharmacokinetics of intravenous mycophenolate mofetil after allogeneic blood stem cell transplantation.

BACKGROUND: Mycophenolate mofetil (MMF) has shown synergistic effects in combination with cyclosporin A (CsA) in prevention of acute graft versus host disease (GvHD) after allogeneic blood stem cell transplantation (BSCT) in preclinical animal models. After having measured low plasma levels of the active metabolite mycophenolic acid (MPA) in recipients of allogeneic blood stem cell transplants after oral administration of MMF, we initiated a phase I/II study evaluating different dose levels of the intravenous (i.v.) formulation together with standard dose CsA. METHODS: A total of 15 patients received i.v. MMF in two split doses for 21 d after allogeneic BSCT from related (n=9) and unrelated (n=6) donors. Total daily doses of 25, 28, 31 and 34 mg/kg were investigated in 3-5 patients at each dose level. Plasma concentrations of MPA and its metabolite mycophenolic acid glucuronide (MPAG) were measured by high-performance liquid chromatography (HPLC). RESULTS: Mean trough blood levels of MPA ranged between 68.8 and 340 ng/mL with a median of 146.7 ng/mL. The mean MPA AUC0-12 h after first dose ranged between 19349+/-5087 ng * h/mL and 25705+/-3042 ng * h/mL and correlated with the dose level of MMF. The incidence of acute GvHD>grade I was 40%. No dose limiting toxicities were observed. CONCLUSIONS: The application of i.v. MMF is safe at a weight-adjusted dose between 25 and 34 mg/kg after allogeneic BSCT. The measured trough blood levels of MPA in patients after BSCT were ten times lower than in healthy volunteers. The toxicity induced by the conditioning therapy seems to negatively influence the pharmacokinetic behavior of MMF, MPA and MPAG.

Successful preemptive cidofovir treatment for CMV antigenemia after dose-reduced conditioning and allogeneic blood stem cell transplantation.

BACKGROUND: Cidofovir (CDV) is a nucleotide analogue with proven in vitro effects against cytomegalovirus (CMV) and adenovirus and has been successfully used in the treatment of CMV retinitis in AIDS patients. METHODS: We performed a prospective study to evaluate the efficacy of CDV in 17 patients with hematological malignancies after allogeneic blood stem cell transplantation from related (n=3) and unrelated (n=14) donors. Dose-reduced conditioning (DRC) regimen consisted of busulfan (Bu)/fludarabine (Flu) (n=9) and idarubicin/cytosine arabinoside/Flu (n=1). Myeloablative conditioning (MC) was performed with Bu/cyclophosphamide (Cy)/etoposide (Eto) (n=4), Bu/Cy (n=2), and total body irradiation (TBI)/Cy/Eto (n=1). Antithymocyte globulin (ATG) was used in seven patients with DRC and in six patients with MC. In all patients, either the donor, host, or both were CMV IgG positive pretransplant. Indication for therapy was preemptive treatment of primary CMV antigenemia defined as two consecutive positive tests of pp65 antigenemia assay after transplant. In case of response with a decreasing number of pp65-positive leukocytes, CDV was scheduled in a dosage of 5 mg/kg body weight once a week for 2 weeks followed by maintenance therapy every 2 weeks in an outpatient setting. All patients received probenecid and prehydration as recommended. Patients were monitored using an immunostaining assay for pp65 antigen and a qualitative and quantitative CMV polymerase chain reaction (PCR). Success of treatment was defined as negativity for the pp65 antigen. RESULTS: After DRC, nine of ten patients (90%) showed a response with seven of nine revealing a complete clearance of the virus (pp65 negative, qualitative PCR negative). In the remaining two responders, treatment was changed to ganciclovir because of either renal impairment or slow clearance of antigenemia. Only one of seven patients in the MC group experienced a temporary clearance of pp65 antigen. After MC, two patients experienced CMV disease. Treatment-related toxicity rate was moderate with four patients developing reversible renal impairment (creatinine 133-180 micromol/L); one patient with proteinuria and three patients with complaints of nausea and vomiting. CONCLUSION: Our data suggest the feasibility of CDV administration in patients after allogeneic transplantation. In the recommended dose, it might be used successfully for low-risk patients, e.g., after DRC or organ transplantation, in an outpatient setting.

Treatment of relapsing leukemia after allogeneic blood stem cell transplantation by using dose-reduced conditioning followed by donor blood stem cells and GM-CSF.

Ten patients with high-risk acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and myelodysplastic syndrome (MDS) relapsing early (< 1 year, n = 8) or late (> or = 1 year, n = 2) after allogeneic transplantation were treated with cytoreductive chemotherapy followed by unmanipulated peripheral blood stem cell transplantation (PBSCT) from related (n = 3) and unrelated donors (n = 7). In order to enhance the graft-versus-leukemia effect, patients received no graft-versus-host disease (GVHD) prophylaxis and granulocyte-macrophage colony-stimulating factor (GM-CSF) was given at a dose of 60 micrograms/m2 after transplant. Acute GVHD grade I-IV was seen in all patients. Eight out of ten patients achieved complete remission: one out of two patients with AML and late relapse is in good condition with limited chronic GVHD more than 1 year after the second PBSCT. The other patient died on day +171 after the second PBSCT from cerebral aspergillosis. One patient with blastic phase CML achieved molecular remission but died +330 days after the second PBSCT because of intracranial bleeding. Of the remaining five patients, three died of infectious complications on days +36, +70, and +27, one patient died with extramedullary relapse on day +35, and one from multi-organ failure in association with acute GVHD on day +32 after the second PBSCT. Two out of ten showed progressive disease and died on days +30 and +90, respectively. Although several patients achieved complete remission, the high risk of GVHD and treatment-related mortality should be kept in mind, especially when a second transplant is considered during a period of less than 12 months after the first procedure. Monitoring of minimal residual disease might predict relapse thus preventing high doses of cytotoxic drugs for reconditioning. The potential of GM-CSF to enhance the graft-versus-leukemia reactivity after cytoreductive therapy for allogeneic transplantation warrants further investigation.

Early allogeneic blood stem cell transplantation after modified conditioning therapy during marrow aplasia: stable remission in high-risk acute myeloid leukemia.

Two patients with high-risk acute myeloid leukemia (AML) whose bone marrow aspirates showed more than 25% blasts between 2 and 4 weeks after the first induction chemotherapy immediately received modified conditioning therapy with intravenous busulfan at 50% of the usual dose and fludarabine, before hematologic recovery occurred. Unmanipulated G-CSF mobilized peripheral blood stem cells from an HLA-identical sibling donor were transfused and haematopoietic recovery was achieved in both recipients. Both of them are in continuing hematological remission with full donor chimerism 12 and 22 months after transplantation. Early treatment intensification with allogeneic cell therapy during marrow aplasia might cure high-risk AML patients who are unlikely to achieve remission with conventional chemotherapy protocols.

Double lumen port access in patients receiving allogeneic blood stem cell transplantation.

We performed a prospective trial investigating the feasibility of a double lumen port access in 26 patients with hematological malignancies or solid tumors receiving either standard conditioning (n = 9, median age 49 years (range 19-65)) or dose-reduced conditioning (n = 17, median age 56 years (range 35-66)) followed by allogeneic blood stem cell transplantation. The port system was implanted within 3 months (n = 20, range 7-91 days) before transplantation or as indicated at different time points after transplantation (n = 6, range 28-680 days). Most infusions, including the graft itself and all blood drawings, were performed via the port. Over a cumulative duration of 5622 days (1310 days after standard conditioning (range 56-349) and 4431 days after dose-reduced conditioning (range 49-489)) two port systems of patients receiving standard conditioning were removed due to early postimplantation pocket infection on day 6 and 8 after insertion, respectively. In the dose-reduced conditioning group only one late removal (day 287) of a port was required. Most of the patients in both groups reported less pain and a higher degree of comfort compared to peripheral or central venipuncture. The use of double lumen port access during conditioning and in an outpatient setting after allogeneic hemopoietic stem cell transplantation is feasible and advantageous for both patient and medical staff. Implantation several weeks before the start of conditioning might help in avoiding early infectious complications after conventional myeloablative conditioning.

The development and assessment of Web-based health information for a corporate Intranet--a pilot study.

Consumers readily use the Internet for medical information, advice and support. Studies of general clinic populations show that moderated internet patient education systems can improve patient satisfaction and affect self help behaviors. Many Americans have Internet access through their employers and large corporations have often developed Intranets for employee information. There is little study of health information available online to employees through company Intranets. This study relates the development of an employer sponsored online health education system, the effects of this system on employee satisfaction with their health care, and the potential effects on worker productivity.

Dose-reduced conditioning for allogeneic blood stem cell transplantation: durable engraftment without antithymocyte globulin.

Between February 1998 and October 1999, 24 patients with advanced leukemia, lymphoma or solid tumors received G-CSF mobilized peripheral blood stem cells (PBSC) from HLA-matched sibling donors after dose-reduced conditioning therapy. Only patients with reduced performance status or major infectious complications, not eligible for standard transplant procedures, were included. The 5-day conditioning therapy consisted of 3.3 mg/kg intravenous busulphan x 2 days and 30 mg/m2 fludarabine x 5 days. GVHD prophylaxis was performed with either CsA alone (n = 5), CsA combined with short course methotrexate (n = 5) or mycophenolate mofetil (n = 14). The day 100 survival was 95.2% for the whole group. All patients engrafted after a median of 15 days (range, 11-19) and 12.5 days (range, 10-19) for neutrophils and platelets, respectively. The median time to a neutrophil count of <0.5 x 109/l was 7 days (range, 2 to 12). Acute GVHD >I was observed in six patients, whereas eight patients have signs of chronic GVHD. The prospective 12 month overall survival with a median follow-up of 7 months is 63%. Relapse of disease and toxicity associated with chronic GVHD were the main causes of death. The treatment-related mortality was 12.5%. Dose-reduced conditioning using intravenous busulphan and fludarabine allows stable engraftment without ATG in related transplants and leads to a reduction of transplant-related mortality.

Diabetes insipidus in a patient with a highly malignant B-cell lymphoma and stomatitis.

A 37-year-old male patient with a diffuse pleomorphic B-cell-lymphoma, which has been diagnosed two month earlier with the primary site at the pterygopalatine fossa on both sides with infiltration of the clivus and cavernous sinus was referred to our hospital for continuation of the third course of CHOP chemotherapy. At admission he reported about a recent history of painful swallowing and intermittent substernal chest pain. Alleviation of the pain on swallowing and the chest pain was apparently only possible by drinking 10 to 15 l of cold coca cola throughout the day and night, a regimen that resulted in polyuria. Physical examination revealed extensive thrush stomatitis and soor esophagitis. Despite successful treatment with fluconazole, polydipsia continued unabated. The classic osmotic test of dehydration and exogenous vasopressin revealed hypothalamic diabetes insipidus (DI). Basal hormones and stimulated endocrine function tests of the adenohypophysis were found to be normal. MRI-scan revealed lymphoma infiltration of the neurohypophysis. After the third course of CHOP chemotherapy the patient surprisingly recovered completely from his excessive thirst. The present report shows that clinical disorders such as thrush stomatitis can mask diabetes insipidus caused by an early relapsing lymphoma.

Treating carpal tunnel syndrome.

UNLABELLED: BACKGROUND CTS is a common problem caused by compression of the median nerve at the wrist resulting in hand numbness, loss of dexterity, muscle wasting, and decreased functional ability at work. This study investigated the efficacy of a corticosteroid injection just proximal (not into) the carpal tunnel for CTS. POPULATION STUDIED: Study participants included 60 patients referred to a neurology clinic in Amsterdam, Netherlands, with CTS symptoms for longer than 3 months' duration and confirmed with electrophysiological tests. Patients in the intervention and control groups had symptoms for an average of 32 months and 25 months, respectively. In patients with bilateral symptoms, the arm with the most severe symptoms was chosen for randomization. Patients aged younger than 18 years and those who had previous treatment for CTS were excluded. STUDY DESIGN AND VALIDITY: Patients were randomized to receive an injection of either lignocaine (Lidocaine 10 mg) and methylprednisolone 40 mg or a lignocaine 10-mg injection only. The site of injection was proximal to the carpal tunnel on the volar side of the forearm 4 cm proximal to the wrist crease, between the tendon of the radial flexor muscle and the long palmar muscle. Injections were given at a 10 degrees to 20 degrees angle with a 3-cm needle. At baseline, there were no significant differences between the control group and the intervention group. The study was performed at one clinic where one neurologist performed all injections. Thus, we do not know if the results of this technique can be consistently reproduced. No patients were reported lost to follow-up at 1 year. To ensure blinding of the treatment assignment, a pharmacist wrapped the syringes in paper and a second neurologist performed outcomes assessment interviews. One month after the initial injection, patients were asked whether they had no symptoms or only minor symptoms that they considered so much improved that they felt no further treatment was necessary. Investigators broke the trial code at follow-up assessment visits to offer nonresponders an injection with methylprednisolone or surgery. OUTCOMES MEASURED: Patients were considered improved if they self-reported no symptoms or only minor symptoms needing no additional treatment. Other symptoms (weakness, nighttime pain) or impact on lifestyle and occupation were not reported. RESULTS: At 1 month, 20% of the patients in the control group had improved compared with 77% of patients in the intervention group (P <.001; number needed to treat = 1.8). After 1 year, 8 of the 23 patients (35%) who initially responded to methylprednisolone required a second injection. A total of 86% of nonresponders in the control group improved after receiving a methylprednisolone injection, but 50% of these patients went on to need surgical treatment within 1 year. The investigators reported no side effects to the injection.

Evaluation of Kromoscopy: resolution of glucose and urea.

Kromoscopy involves the transmission of a broad band of electromagnetic radiation through the sample of interest. The transmitted light is collected and divided evenly into four detector channels with complementary bandpass functions. This optical configuration provides high signal-to-noise ratios that are ideal for analytical measurements. The molecular basis of the four-channel response is critical, because it directly influences selectivity of the measurement and, therefore, the feasibility of applications in complex sample matrices. Selectivity of the Kromoscopic signal is demonstrated by resolution of glucose and urea with four channels of information collected over the 800-1300-nm near-infrared spectral region. Analysis of the individual channel responses indicates that the displacement of water from the optical path by the dissolution of solute is a major component of the Kromoscopic measurement in this spectral region. Nevertheless, significant differences are observed in channel responses for glucose and urea. A three-dimensional vector plot of the data highlights these differences and reveals unique vector directions for glucose and urea. This difference in direction of the response vectors represents the principal basis for distinguishing glucose and urea dissolved in aqueous solutions.

An office-based Internet patient education system: a pilot study.

BACKGROUND: Patients' use of the Internet to find medical information is increasing, and physicians are exploring ways to incorporate the Internet into patient education programs and physician-patient encounters. We performed a pilot study of an Internet patient education system to obtain information on the usefulness of, feasibility of, and patient satisfaction with this type of information. METHODS: We developed a hypertext Web page directory to patient education sites on the Internet and made it available to patients in a community-based family practice residency clinic during their office visit. During a 1-month period, a medical student assisted patients with using the Internet, answered questions, interviewed patients, and collected data. Information was collected on sites visited, level of assistance required, amount of time spent "surfing" on-line versus intense reading on-line, quality of the experience, perceived usefulness of the educational materials, and patients' satisfaction with the materials. RESULTS: Fifty patients participated in the study. Forty-seven patients (94%) found the Internet information helpful. Most patients spent their time on-line intensely reading, and men spent significantly more time on-line (P = .007). Thirty-seven patients (77%) stated they would change a health behavior because of information they had read on the Internet; 45 (90%) were more satisfied with their visit than usual, and 46 (92%) would use the Internet center at the clinic again. CONCLUSIONS: Patients can obtain useful information from moderated Internet patient education systems and may plan to change health behaviors on the basis of that information. Internet patient information in the physician's office can improve patient satisfaction with clinic visits.

Bacterial vaginosis in pregnancy and the risk of prematurity: a meta-analysis.

OBJECTIVE: We conducted this meta-analysis to determine the magnitude of risk conferred by bacterial vaginosis during pregnancy on preterm delivery. SEARCH STRATEGY: We selected articles from a combination of the results of a MEDLINE search (1966-1996), a manual search of bibliographies, and contact with leading researchers. SELECTION CRITERIA: We included case control and cohort studies evaluating the risk of preterm delivery, low birth weight, preterm premature rupture of membranes, or preterm labor for pregnant women who had bacterial vaginosis and those who did not. DATA COLLECTION AND ANALYSIS. Two investigators independently conducted literature searches, applied inclusion criteria, performed data extraction, and critically appraised included studies. Summary estimates of risk were calculated as odds ratios (ORs) using the fixed and random effects models. MAIN RESULTS: We included 19 studies in the final analysis. Bacterial vaginosis during pregnancy was associated with a statistically significant increased risk for all outcomes evaluated. In the subanalyses for preterm delivery, bacterial vaginosis remained a significant risk factor. Pooling adjusted ORs yielded a 60% increased risk of preterm delivery given the presence of bacterial vaginosis. CONCLUSIONS: Bacterial vaginosis is an important risk factor for prematurity and pregnancy morbidity. Further studies will help clarify the benefits of treating bacterial vaginosis and the potential role of screening during pregnancy.

Smoking cessation intervention: the practices of maternity care providers.

BACKGROUND: Little is known about the actual smoking intervention practices of maternity care providers. This study examines smoking intervention practices of maternity care providers in a large Midwestern city. METHODS: A telephone survey was used to collect information on the care of pregnant patients who smoke (n = 73). RESULTS: After brief counseling during the first prenatal care visit (98 percent), 84 percent of providers readdressed smoking at follow-up visits. Family physicians were significantly more likely than obstetricians to provide further counseling (97 versus 72 percent, P < 0.005). Common cessation interventions included provider counseling (99 percent) and recommending smoking cessation classes (26 percent). Reasons cited by providers for patients' inability to stop smoking during pregnancy included addiction, habit, and environment or family. Methods used to encourage smoking cessation did not correlate with those known to be effective for treating addiction, modifying behavior, or responding to family or social system problems. CONCLUSION: Maternity care providers underutilize effective methods of smoking cessation for their patients who smoke and rely on less effective methods.

Residents find clinical practice guidelines valuable as educational and clinical tools.

BACKGROUND AND OBJECTIVES: Information regarding clinical practice guideline (CPG) use in residency education is limited. We surveyed a regional population of family practice residents to determine use, attitudes, and curricular needs for practice guidelines. METHODS: A written survey was developed that measured residents' exposure to, frequency of use, attitudes, access, and knowledge about use of CPGs. The survey was mailed to 114 family practice residents. RESULTS: The response rate was 75%. The most frequently seen guidelines were immunization schedules, cancer screening, hyperlipidemia, and hypertension management. The residents reported positive attitudes toward CPGs; 75% thought CPGs were easy to use, 80% thought they improved their efficiency, 78% thought they improved their residency education, and 75% thought they improved patient care. Barriers to effective use of practice guidelines were also identified; 20% knew where to find guidelines in their clinic, 35% had faculty modeling, and 22% knew how to evaluate the validity of a guideline. Eighty-nine percent of respondents desired instruction on CPG use and interpretation. CONCLUSIONS: The surveyed family practice residents have similar usage rates for CPGs as the literature reports for practicing physicians, but residents report more positive attitudes. Barriers that prevent effective use of CPGs in training environments include lack of critical appraisal abilities and faculty role modeling.

[Pulmonary artery stenosis in aggressive mediastinal fibrosis; diagnosis and 3D imaging with helical CT examination]. / Pulmonalarterienstenose bei aggressiver Mediastinalfibrose; Diagnostik und 3D-Darstellung mittels helikaler CT-Untersuchung.

An aggressive mediastinal fibrosis was found in a 42-year-old female, suffering from dysphagia, stabbing pain in the chest, and an unclear weight loss. In this case, the rare combination of esophageal involvement, bronchial narrowing, and pulmonary artery obstruction could easily be demonstrated with a barium study and a helical CT examination including three-dimensional reconstructions.