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C Jacobs

Publications and source records attributed to C Jacobs.

At least 55 records · Page 3Linked to original sources

Nanosuspensions as a new approach for the formulation for the poorly soluble drug tarazepide.

Poorly soluble drugs are often a challenging problem in drug formulation, especially when the drug is not soluble in either aqueous media or organic solvents. Attempts to overcome the solubility problem are, e.g. solubilisation with mixed micelles or forming a complex using cyclodextrines, but these approaches are of limited success. Another problem with new high potential drug is that these drugs often show bioavailability problems. One tried to improve the in vivo performance of poorly soluble drugs by reducing the particles size of the drug thus leading to an increased surface area and an increased dissolution velocity (Müller et al., 1994, 1999). Some of these problems occurred with tarazepide and therefore it was tried to create a formulation with this drug as nanosuspension which is suitable for intravenous administration.

Benzodiazepines↗

The visual display of regulatory information and networks.

Cell regulation and signal transduction are becoming increasingly complex, with reports of new cross-signalling, feedback, and feedforward regulations between pathways and between the multiple isozymes discovered at each step of these pathways. However, this information, which requires pages of text for its description, can be summarized in very simple schemes, although there is no consensus on the drawing of such schemes. This article presents a simple set of rules that allows a lot of information to be inserted in easily understandable displays.

Audiovisual Aids↗

Human herpesvirus 8 (KSHV) contamination of peripheral blood and autograft products from multiple myeloma patients.

Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV), has recently been identified within the bone marrow dendritic cells of multiple myeloma (MM) patients. This virus contains homologues to human cytokines such as IL-6 that could potentially stimulate myeloma cell growth and contribute to disease pathogenesis. Since mobilization chemotherapy may increase circulating dendritic cell numbers, we searched for HHV-8 in peripheral blood mononuclear cells (PBMCs) before and after mobilization chemotherapy given to MM patients. Furthermore, we determined if autograft purging using the CEPRATE SC device would reduce the percentage of HHV-8 infected stem cell products. Only two of the 39 PBMC samples collected prior to mobilization chemotherapy contained PCR detectable virus, yet nine of 37 PBMCs collected on the first day of leukapheresis had detectable HHV-8 (P = 0.016). HHV-8 was more frequently identified in autograft products before vs after Ceprate SC selection (40% vs 15%, P = 0.016). Although the role HHV-8 plays in myeloma pathogenesis remains unclear, these results imply that mobilization chemotherapy increases the numbers of circulating HHV-8-infected dendritic cells within the peripheral blood. In addition, CD34 selection of autograft products in MM patients may reduce the reintroduction of virally infected cells following high-dose chemotherapy. Bone Marrow Transplantation (2000) 25, 153-160.

Antigens, CD34↗

Managers forum

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Journal Article↗

Effect of physical therapy on limited joint mobility in the diabetic foot. A pilot study.

Eleven patients with limited joint mobility and neuropathy were enrolled in a physical therapy program of passive joint mobilization at a rate of two sessions per week. Treatment resulted in a significant improvement in joint mobility after 10 sessions. Further improvement after 20 sessions did not reach the level of statistical significance, although near-normal joint mobility was attained. After completion of therapy, there was a progressive deterioration in joint mobility. No serious adverse effects were noted during treatment. This study provides some evidence that use of physical therapy may result in significant, although temporary, improvement in the mobility of the ankle and foot joints in diabetic patients with limited joint mobility and neuropathy. As limited joint mobility has been associated with the development of abnormally high pressures under the feet, which in turn may contribute to plantar ulceration in the susceptible neuropathic foot, the results indicate that physical therapy may be useful in the prevention of plantar ulceration in diabetic patients with limited joint mobility and neuropathy, although this must be verified by additional research.

Adult↗

Retroperitoneal fibrosis and membranous nephropathy.

We report on a patient with a past history of Pott's abscess who suffered both from a retroperitoneal fibrosis and a membranous glomerulonephritis. Five cases of retroperitoneal fibrosis and immune complex glomerulonephritis are already reported in the literature. These associations might result from a particular systemic immune response to an unknown antigen. Consequently, we consider the role of tuberculosis in our case.

Adult↗

Bridging the gap between conventional and alternative medicine.

BACKGROUND: The use of various forms of complementary and alternative medicine (CAM) has become widespread. We investigated this use in Madison, Wisconsin. METHODS: We conducted semistructured indepth interviews focused on the knowledge, attitudes, and behaviors of a random sample of 17 patients who had used both CAM and conventional therapies during the past year. Participants were recruited using telephone listings. Twenty alternative practitioners were selected to represent the major modalities. The topics discussed included healing philosophy, choices of therapeutic methods, and ideas concerning concurrent use of differing therapeutic modalities. An 8-member multidisciplinary team analyzed the transcripts individually and in group meetings. RESULTS: Four major themes emerged from the interview data: (1) holism, (2) empowerment, (3) access, and (4) legitimization. Both patients and providers distinguished between the socially legitimized and widely accessible but disempowering and mechanistic attributes of conventional medicine and the holistic and empowering but relatively less accessible and less legitimate nature of alternative healing. There was a strong call for integrating the best aspects of both. CONCLUSIONS: Practitioners and users of alternative therapies in the Madison area confirmed both the alternative and complementary natures of unconventional health care, called for more integrated and accessible health care, and provided insights that could be useful in bridging the gap between conventional and alternative medicine.

Attitude of Health Personnel↗

[Phamacokinetics of low-molecular-weight heparins Fragmin D in dogs].

The pharmacokinetics of a low molecular weight heparin (LMWH; Fragmin D) was studied in dogs after intravenous and subcutaneous administration, based on antifactor Xa- (anti-fXa-) activity. Each dosage was examined in 5 adult Beagles. After intravenous application of 25, 50 and 100 anti-fXaU./kg body weight (BW) the mean peak plasma heparin activity of 0.52 +/- 0.12 (x +/- s), 1.08 +/- 0.23 and 1.86 +/- 0.17 anti-fXaU./ml, respectively, was measured. After subcutaneous application of 50, 100 and 200 anti-fXaU./kg BW maximum heparin activity in the plasma was determined after 144-216 minutes (mean values) of 0.28 +/- 0.01, 0.52 +/- 0.06 or 1.09 +/- 0.20 anti-fXaU./ml. Intravenous application of LMWH has a short plasma terminal half-life (t50) between 49 and 76 minutes which depended on the dosage. After administration of 50 anti-fXaU./kg BW (74 minutes) and 100 anti-fXaU./kg BW (76 minutes) no essential difference was shown. A distinctly longer t50 was found after subcutaneous injection. After injection of 50, 100 and 200 anti-fXaU./kg BW t50 values of 81, 123 and 182 minutes were calculated. According to this, with increasing dosage a decrease of the total clearance was found for both application routes. The apparent volume of distribution after intravenously applicated LMWH ranged between 50 and 70 ml/kg BW. The absolute bioavailability calculated for the subcutaneous NMH-injection of 50 and 100 anti-fXaU./kg BW was 107% and 104%, respectively.

Animals↗

Binding of 14-3-3beta to the carboxyl terminus of Wee1 increases Wee1 stability, kinase activity, and G2-M cell population.

Wee1 protein kinase plays an important regulatory role in cell cycle progression. It inhibits Cdc-2 activity by phosphorylating Tyr15 and arrests cells at G2-M phase. In an attempt to understand Wee1 regulation during cell cycle, yeast two-hybrid screening was used to identify Wee1-binding protein(s). Five of the eight positive clones identified encode 14-3-3beta. In vivo binding assay in 293 cells showed that both full-length and NH2-terminal truncated Wee1 bind with 14-3-3beta. The 14-3-3beta binding site was mapped to a COOH-terminal consensus motif, RSVSLT (codons 639 to 646). Binding with 14-3-3beta increases the protein level of full-length Wee1 but not of the truncated Wee1. Accompanying the protein level increases, the kinase activity of Wee1 also increases when coexpressed with 14-3-3beta. Increased Wee1 protein level/enzymatic activity is accountable, at least in part, to an increased Wee1 protein half-life when coexpressed with 14-3-3beta. The protein half-life of the NH2-terminal truncated Wee1 is much longer than that of the full-length protein and is not affected by 14-3-3beta cotransfection. Biologically, 14-3-3beta/Wee1 coexpression increases the cell population at G2-M phase. Thus, Wee1 binding with 14-3-3beta increases its biochemical activity as well as its biological function. The finding reveals a novel mechanism by which 14-3-3 regulates G2-M arrest and suggests that the NH2-terminal domain of Wee1 contains a negative regulatory sequence that determines Wee1 stability.

14-3-3 Proteins↗

[Preservation of vascular and cardiac capital in the patient with chronic kidney failure].

Preservation of the vascular and cardiac capital is an essential objective at all times in patients with chronic renal failure, even before end-stage renal failure, at which time the urologist may need to perform surgical procedures on the urinary tract in the presence of uropathy. Medical and paramedical teams must be aware of the importance of preservation of the capital venous of the upper extremity and the risks of subclavian catheterization at this stage. When creating a vascular access, distal anastomoses should be preferred, sometimes at the cost of grafting, in order to preserve left ventricular function. Close collaboration with radiologists is now essential to manage complications of vascular accesses. The management of arteriovenous fistula after transplantation depends on many sometimes contradictory parameters and should be determined case by case. The importance of "economic" management of the patient's vascular and cardiac capital justifies global management of chronic renal failure by urologists perfectly familiar with the specific problems of these patients and trained to intervene throughout the course of the disease.

Cardiovascular Diseases↗