Remotely-delivered cognitive remediation in multiple sclerosis (MS): protocol and results from a pilot study.

BACKGROUND: Cognitive impairment represents a critical unmet treatment need in multiple sclerosis (MS). Cognitive remediation is promising but traditionally requires multiple clinic visits to access treatment. Computer-based programs provide remote access to intensive and individually-adapted training. OBJECTIVE: Our goal was to develop a protocol for remotely-supervised cognitive remediation that enables individuals with MS to participate from home while maintaining the standards for clinical study. METHODS: MS participants (n = 20) were randomized to either an active cognitive remediation program (n = 11) or a control condition of ordinary computer games (n = 9). Participants were provided study laptops to complete training for five days per week over 12 weeks, targeting a total of 30 hours. Treatment effects were measured with composite change via scores of a repeated neuropsychological battery. RESULTS: Compliance was high with an average of 25.0 hours of program use (80% of the target) and did not differ between conditions (25.7 vs. 24.2 mean hours, p = 0.80). The active vs. control participants significantly improved in both the cognitive measures (mean composite z-score change of 0.46 ± 0.59 improvement vs. -0.14 ± 0.48 decline, p = 0.02) and motor tasks (mean composite z-score change of 0.40 ± 0.71improvement vs. -0.64 ± 0.73 decline, p = 0.005). CONCLUSIONS: Remotely-supervised cognitive remediation is feasible for clinical study with potential for meaningful benefit in MS.

Fabrication and mechanical properties of PLLA/PCL/HA composites via a biomimetic, dip coating, and hot compression procedure.

Currently, the bone-repair biomaterials market is dominated by high modulus metals and their alloys. The problem of stress-shielding, which results from elastic modulus mismatch between these metallic materials and natural bone, has stimulated increasing research into the development of polymer-ceramic composite materials that can more closely match the modulus of bone. In this study, we prepared poly(L: -lactic acid)/hydroxyapatite/poly(epsilon-caprolactone) (PLLA/HA/PCL) composites via a four-step process, which includes surface etching of the fiber, the deposition of the HA coating onto the PLLA fibers through immersion in simulated body fluid (SBF), PCL coating through a dip-coating process, and hot compression molding. The initial HA-coated PLLA fiber had a homogeneous and continuous coating with a gradient structure. The effects of HA: PCL ratio and molding temperature on flexural mechanical properties were studied and both were shown to be important to mechanical properties. Mechanical results showed that at low molding temperatures and up to an HA: PCL volume ratio of 1, the flexural strain decreased while the flexural modulus and strength increased. At higher mold temperatures with a lower viscosity of the PCL a HA: PCL ratio of 1.6 gave similar properties. The process successfully produced composites with flexural moduli near the lower range of bone. Such composites may have clinical use for load bearing bone fixation.

Influence of pretreatment on the surface characteristics of PLLA fibers and subsequent hydroxyapatite coating.

A fibrous precursor for bone repair composites was made by coating poly(L-lactide) (PLLA) fibers with hydroxyapatite (HA) using a biomimetic method. To enhance the bonding between the HA coating and the PLLA fiber, PLLA fibers were etched with either sodium hydroxide or sodium hypochlorite to generate carboxyl groups on fiber surfaces. The experiments were designed to determine the influence of etching on the fiber surface morphology and chemistry as well as the subsequent HA coating on the etched fiber surfaces. It was found that the etching pretreatment increased the roughness as well as the hydrophilicity of fibers, indicating that hydrolysis of PLLA chains had taken place on fiber surfaces. The etching pretreatment also promoted HA coating formation by introducing thicker coating on the surface of fibers with a longer etching time, a higher etching concentration, or with NaOCl as the etching agent. A mechanism of surface hydrolysis and oxidation of PLLA was proposed.

Travelling to China for the Beijing 2008 Olympic Games.

The Beijing Olympics will be the world's premier sporting event in 2008. Countries should begin planning for appropriate support for their Olympic athletes. Experienced medical staff should be appointed early and become familiar with the major medical or injury concerns of athletes and officials. Teams should assemble a comprehensive medical kit. Appropriate medical advice can ensure that athletes will arrive in Beijing in optimal condition. Medical issues particularly relevant to competitors at the Beijing Olympics include heat and humidity, waterborne diseases and air pollution. However, the air pollution probably represents less of a threat than previous media reports would indicate. The Olympic village and venues can be thought of as small enclaves located within a rapidly developing country.

Influence of temperature and aging time on HA synthesized by the hydrothermal method.

The influence of temperature and aging time on the morphology and mechanical properties of nano-sized hydroxyapatite (HA) synthesized by a hydrothermal method is reported here. The pre-mixed reactants were poured into a stirred autoclave and reacted at temperatures between 25-250 degrees C for 2-10 h. HA powders thus obtained were examined using X-ray diffraction (XRD), high-resolution field emission scanning electron microscopy (FESEM) and a particle size analyzer. It was found that the aspect ratio of the particles increased with the reaction temperature. The length of the HA particles increased with the reaction temperature below 170 degrees C, but it decreased when the temperature was raised above 170 degrees C. The agglomerates of HA particles were formed during synthesis, and their sizes were strongly dependent on reaction temperatures. As the reaction temperature increased, the agglomerate size decreased (p = 0.008). The density of the discs pressed from these samples reached 85-90% of the theoretical density after sintering at 1200 degrees C for 1 h. No decomposition to other calcium phosphates was detected at this sintering temperature. A correlation existed (p = 0.05) between the agglomerate sizes of HA particles synthesized at various conditions and their sintered densities. With the increase of the agglomerate size, the sintered density of the HA compact decreased. It was found that both the sintered density and flexural strength increased with increasing aging time and reaction temperature. A maximum flexural strength of 78 MPa was observed for the samples synthesized at 170 degrees C for 5 h with the predicted average at these conditions being 65 MPa. These samples attained an average sintered density of 88%.

Cutaneous Hodgkin's disease in a patient with human immunodeficiency virus infection.

A 22-year-old man with human immunodeficiency virus infection had skin nodules of the chest wall. When a biopsy was performed on these nodules, Hodgkin's disease was discovered. The patient was subsequently found to have widespread disease involving the lymph nodes and liver. Skin involvement with Hodgkin's disease is rare. In this report, we review previous descriptions of skin involvement appearing in the literature.

5-Fluorouracil, doxorubicin, and mitomycin-C in the treatment of adenocarcinoma and large cell carcinoma of the lung.

Fifty-four patients with adenocarcinoma and large cell carcinoma of the lung, 16 with localized surgically resected disease and 38 with metastatic disease, were treated with 5-fluorouracil, doxorubicin, and mitomycin-C (FAM), in an attempt to prolong previously reported survival times in the patients. The postsurgical patients were given elective chemotherapy. Eighteen received radiation therapy for control of local disease. Tumor regression, attributable to chemotherapy alone, was noted in ten of 20 cases in whom there was measurable disease. The median survival time of all patients was 32 weeks, ranging from 25 weeks in those with distant metastases to 56 weeks in patients with surgically resected disease. FAM did not seem to produce any beneficial survival advantages.

Oat cell carcinoma of the esophagus: unusual radiological appearances.

Primary oat cell carcinoma of the esophagus is a very rare tumour. The radiographic appearance of the three cases described in this paper are unusual because they resemble benign lesions such as leiomyoma, fibrous polyp and candidiasis. It would be interesting to investigate whether such an unusual appearance is common for this neoplasm.

Clinical trials with diglycoaldehyde (NSC-118994): review and reasons for withdrawal from clinical trial.

All Phase II studies with diglycoaldehyde with leukemia and solid tumors have been reviewed. The dose schedules employed ranged from 1.5 to 2.0 g/m2/day for 3 to 5 days. The most common side effects have been gastrointestinal (nausea and vomiting), which occurred in 22% of the patients. Renal toxicity (rise in BUN, creatinine, and urinary proteins) was seem in 17% of the patients treated. Other infrequent toxicities include hypocalcemia (9%) and local complications such as phlebitis. Leukopenia, thrombocytopenia, positive Coombs' test and impairment in coagulation profile were also reported. In contrast to the hints of therapeutic efficacy described during Phase I trials, in phase II trials no activity was noted among 96 patients with solid tumors and only minimal antileukemic action among 49 other patients. These disappointing Phase II trials coupled with prominent toxicities have prompted the decision to terminate further clinical testing. This report summarizes all clinical observations as an example of circumstances which curtail clinical testing of anticancer drugs.

Monocytic leukemias.

The monocytic leukemias may be subdivided into acute monocytic leukemia, acute myelomonocytic leukemia, and subacute and chronic myelomonocytic leukemia. The clinical features of acute monocytic and acute myelomonocytic leukemias are similar and are manifestations of bone marrow failure. Gingival hypertrophy and skin infiltration are more frequent in acute monocytic leukemia. Cytomorphologically the blast cells in acute monocytic leukemia may be undifferentiated or differentiated, whereas in the acute myelomonocytic variety there are mixed populations of monocytic and myeloblastic cells. Cytochemical characteristics include strongly positive reactions for nonspecific esterase, inhibited by fluoride. The functional characteristics of acute monocytic and acute myelomonocytic cells resemble those of monocytes and include glass adherence and phagocytoses, the presence of Fc receptors for IgG and C'3, and the production of colony stimulating activity. Subacute and chronic myelomonocytic leukemias are insidious and slowly progressive diseases characterized by anemia and peripheral blood monocytosis. Atypical monocytes called paramyeloid cells are characteristic. The drugs used in the treatment of acute monocytic and acute myelomonocytic leukemias include cytosine arabinoside, the anthracyclines, and VP 16-213. Drug therapy in subacute and chronic myelomonocytic leukemias is not usually indicated, although VP 16-213 has been claimed to be effective.

Baker's antifol in combination with 5-fluorouracil and methyl-CCNU in the treatment of metastatic colorectal cancer: a Southwest Oncology Group Study (Protocol 7764).

Fifty-one previously untreated patients with metastatic colorectal cancer were treated with a combination of 5-fluorouracil, methyl-CCNU, and Baker's antifol. Six of 34 fully evaluable patients achieved a response. There were no apparent benefits obtained with this combination compared to treatment with 5-fluorouracil alone.

Phase I clinical studies with WR-2721.

Toxicity studies of S-2-(3 aminopropylamino)-ethylphosphorothioic acid (WR-2721) access patients in remission following radiation therapy. The dose has been escalated from 25 to 250 mg/m2 without significant symptoms. Inconsistent variation in the systolic blood pressure in some patients has been observed over an 8-10-point range without producing any symptoms. The variation could be within the patient's normal range. However, tests are planned to rule out cardiac toxicity or peripheral vascular reaction. Combining WR-2721 with conventional radiotherapy is contemplated by intravenous injection of the drug 20-30 minutes before irradiation. This will start as weekly injections, and the number of weekly injections will be increased progressively. Animal studies suggest that the level already safely reached could give significant protection to the normal tissues without protecting tumor.

Reinduction therapy for adult acute leukemia with adriamycin, vincristine, and prednisone: a Southwest Oncology Group study.

In an attempt to improve remissions and survivals in previously treated patients with adult acute leukemia, we gave Adriamycin, vincristine, and prednisone for induction therapy, followed by 6-mercaptopurine and methotrexate for maintenance therapy to patients attaining complete remission (CR). The study group consisted of 18 patients with acute myeloblastic leukemia (AML), ten with acute lymphoblastic leukemia, and one with acute undifferentiated leukemia. Only one patient had previously received Adriamycin. Overall, there were ten CRs and two partial remissions. The five CRs and one partial remission in patients with AML occurred among those with one prior induction attempt; none of the eight AML patients with more than one prior induction attempt responded. The actuarial median duration of CR was 15 weeks and was similar for AML and acute lymphoblastic leukemia patients. Responders had a longer median survival (30 weeks) than nonresponders (9 weeks). Thus, although a reasonable number of responses in previously treated patients were obtained with this program, improvements in maintenance therapy are clearly needed.

Capillary viscometer for use with crosslinking polymer melts.

A capillary viscometer is described which adapts a conventional capillary rheometer for use with crosslinking polymers. Illustrative data obtained with the viscometer using diallyl phthalate resin are included.