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.

Serial analysis of circulating adhesion molecules and TNF receptor in serum from patients with multiple sclerosis: cICAM-1 is an indicator for relapse.

We determined the serum levels for circulating adhesion molecules (circulating intercellular adhesion molecule-1 [cICAM-1], circulating endothelial leukocyte adhesion molecule-1 [cELAM-1], and circulating L-selectin [cL-selectin]) and circulating tumor necrosis factor receptor (cTNF-R) p60 in 29 patients with relapsing-remitting MS serially over a period of 12 months. During this period there were 27 relapses in 14 patients (48%). There was progression of disease activity in 12/25 patients (48%), as assessed by the occurrence of new lesions on nonenhancing, T2-weighted MRIs of the head. Clinically active patients with relapse or disease progression on MRI (n = 18) had frequent fluctuations in their serum levels for cICAM-1 if compared to patients with stable MS (n = 11). There were significant differences in the cumulative cICAM-1 production between the two groups (502 +/- 218 ng/ml in active versus 225 +/- 82 ng/ml in stable MS patients; p < 0.001). cTNF-R p60 serum levels were higher in patients with stable compared to active disease (2.3 +/- 0.5 ng/ml versus 1.5 +/- 0.6 ng/ml; p < 0.005). A significant increase in cICAM-1 levels was present at the time of a relapse (799 +/- 263 ng/ml versus 449 +/- 95 ng/ml; p < 0.001), whereas the highest serum levels for cTNF-R p60 occurred 4 weeks after the onset of a relapse (1.8 +/- 0.5 ng/ml at relapse versus 2.3 +/- 0.6 ng/ml 4 weeks after a relapse; p < 0.01). Interestingly, the cL-selectin serum levels in all MS patients were significantly higher than in healthy donors, whereas there were no differences for cELAM-1. These results reflect distinct changes of inflammatory variables in serum of patients with MS and revealed that cICAM-1 is an indicator for disease activity and that high serum levels for cTNF-R p60 are associated with remission.

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.

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.

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.

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.

Quantitative image analysis of vertebral body architecture--improved diagnosis in osteoporosis based on high-resolution computed tomography.

71 women, 64 post-menopausal, were examined by single-energy quantitative computed tomography (SEQCT) and by high-resolution computed tomography (HRCT) scans through the middle of lumbar vertebral bodies. Computer-assisted image analysis of the high-resolution images assessed trabecular morphometry of the vertebral spongiosa texture. Texture parameters differed in women with and without age-reduced bone density, and in the former group also in patients with and without vertebral fractures. Discriminating parameters were the total number, diameter and variance of trabecular and intertrabecular spaces as well as the trabecular surface (p < 0.05)). A texture index based on these statistically selected morphometric parameters identified a subgroup of patients suffering from fractures due to abnormal spongiosal architecture but with a bone mineral content not indicative for increased fracture risk. The combination of osteodensitometric and trabecular morphometry improves the diagnosis of osteoporosis and may contribute to the prediction of individual fracture risk.

Immunoscintigraphy for the detection of brain abscesses.

The aim of this prospective study was to assess the diagnostic usefulness of a 99Tcm-anti-granulocyte antibody in the early differentiation of the aetiology of a ring-enhancing structure on computed tomography (CT) scans following neurosurgical intervention. In 26 patients (15 males, 11 females) aged 20-82 years with suspected intracranial infection, 29 SPET scans of the head were obtained 4-6 h following the intravenous injection of 555 MBq 99Tcm-anti-granulocyte antibody. The patients had antibiotic, antimycotic or corticosteroid therapy. The diagnosis was confirmed by surgery (19 cases) or subsequent CT/MRI (magnetic resonance imaging) scans and clinical follow-up (10 cases). The immunoscan was true-positive (abscess) in 6 (sensitivity = 100%), true-negative in 19 and false-positive in 4 (specificity 83%) cases. There was no obvious detrimental effect on the results due to the antibiotic, antimycotic or corticosteroid therapy. In conclusion, despite false-positive results, the 99Tcm-anti-granulocyte antibody is a useful tool in the early detection and exclusion of intracranial abscess after neurosurgical interventions.

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.

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.

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.

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.

[The significance of anticipating suspected brain death for the accusation of failure to treat according to Section 323c of the Federal Penal Code]. / Die Bedeutung einer antezipierten Hirntodvermutung für den Vorwurf unterlassener Hilfeleistung gem. Section 323 c StGB.

Brain death is usually not confirmed by neurological and angiographical techniques until long after it has actually taken place. In connection with a case in which expert testimony was heard, clinical and radiographic evidence and the autopsy statement are discussed as criteria of continuing development of brain edema; on the basis of the evidence it was possible to conclude that the cerebral circulation had not yet ceased at the time assumed.

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.