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Biomedical subjects

R David

Publications and source records attributed to R David.

At least 19 recordsLinked to original sources
PubMed2006

[Embryonic stem cells. Future perspectives].

Embryonic stem cells (ES cells) are able to differentiate into any cell type, and therefore represent an excellent source for cellular replacement therapies in the case of widespread diseases, for example heart failure, diabetes, Parkinson's disease and spinal cord injury. A major prerequisite for their efficient and safe clinical application is the availability of pure populations for direct cell transplantation or tissue engineering as well as the immunological compatibility of the transplanted cells. The expression of human surface markers under the control of cell type specific promoters represents a promising approach for the selection of cardiomyocytes and other cell types for therapeutic applications. The first human clinical trial using ES cells will start in the United States this year.

Cells, Cultured↗
PubMed2006

Differential effects of immunosuppressive drugs on T-cell motility.

The best-characterized mechanism of the action of immunosuppressive drugs is to prevent T-cell clonal expansion, thus containing the magnitude of the ensuing immune response. As T-cell recruitment to the inflammatory site is another key step in the development of T-cell-mediated inflammation, we analyzed and compared the effects of two commonly used immunosuppressants, cyclosporin A (CsA) and the rapamycin-related compound SDZ-RAD, on the motility of human CD4+ T cells. We show that CsA, but not SDZ-RAD, inhibits T-cell transendothelial migration in vitro. CsA selectively impaired chemokine-induced T-cell chemotaxis while integrin-mediated migration was unaffected. The inhibition of T-cell chemotaxis correlated with reduced AKT/PKB but not ERK activation following exposure to the chemokine CXCL-12/SDF-1. In addition, CsA, but not SDZ-RAD, prevents some T-cell receptor-mediated effects on T-cell motility. Finally, we show that CsA, but not SDZ-RAD inhibits tissue infiltration by T cells in vivo. Our data suggest a prominent antiinflammatory role for CsA in T-cell-mediated tissue damage, by inhibiting T-cell trafficking into tissues in addition to containing clonal expansion.

Animals↗
PubMed2006

Progression of autoimmune diabetes: slowly progressive insulin-dependent diabetes mellitus or latent autoimmune diabetes of adult.

Autoimmune diabetes is due to destruction of insulin-secreting beta islet cells by an immune-mediated process, which is induced and promoted by the interaction of genetic and environmental factors. This form of diabetes is one of a group of autoimmune diseases that affect about 10% of the population in the developed world. The detection of diabetes-associated autoantibodies, including glutamic acid decarboxylase antibodies (GADA), islet cell antibodies (ICA), and insulinoma-associated (IA-2) autoantibodies is widely held to reflect an underlying autoimmune pathology but the clinical features associated with the presence of these diabetes-associated autoantibodies is highly variable ranging from lack of symptoms with normal glucose tolerance to catastrophic and potentially fatal diabetic ketoacidosis. It is the purpose of this article to establish the range of metabolic features associated with diabetes-associated autoimmune changes and discuss how this metabolic spectrum itself reflects a spectrum of immune and clinical changes that cast light on the nature of autoimmune diabetes.

Adult↗
PubMed2004

Length of stay in hospital following spinal cord lesions in Israel.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To monitor length of stay (LOS) in a specialist spinal cord lesion (SCL) department in Israel, evaluate factors that affect it, and assess its association with other outcome measures. SETTING: Loewenstein Rehabilitation Hospital, Raanana, Israel. METHODS: In all, 1367 SCL patients treated between 1962 and 2000, and a group of 44 patients admitted between 1996 and 2002 were recruited. LOS, factors that affect it, and Spinal Cord Independence Measure second version (SCIM-II) gain and efficiency were measured. Data were collected from hospital charts and from the Population Registry of the Israel Ministry of Internal Affairs. LOS associations were analyzed with ANOVA, ANCOVA, Pearson's chi(2) test, Pearson's correlation, and Cox proportional hazard model. RESULTS: The mean LOS was 239 days for traumatic SCL (SD=168) and 106 days for non-traumatic SCL (SD=137). SCL etiology, SCL severity, and decade of admission to rehabilitation, were associated with the LOS (P<0.001). SCIM II gain correlated with LOS in the first 70 days after admission (r=0.81-0.82; P<0.001). In some patients, longer LOS was associated with a considerable increase in ability, through 5-8 months from admission. CONCLUSIONS: LOS of patients with SCL in Israel is within the customary LOS range in Europe. Longer LOS in a specialist SCL department may be positively associated with improved rehabilitation outcome. Further study is required to determine the LOS that allows optimal achievements.

Adolescent↗
PubMed2004

Outcomes in patients admitted for rehabilitation with spinal neurological lesions following intervertebral disc herniation.

BACKGROUND: Little information is available about the survival, neurological recovery, and length of stay in hospital for rehabilitation (LOS) of patients with spinal neurological deficit following disc herniation (DH). STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To report on outcomes and factors affecting these. SETTING: The Spinal Research Laboratory, Loewenstein Rehabilitation Hospital, Israel. SUBJECTS: A total of 158 patients with DH spinal neurological lesions (DHSNL). METHOD: Data were collected retrospectively. Survival was assessed using the Kaplan-Meier method; relative mortality risk by the Cox proportional hazard model. Neurological recovery was evaluated by calculating the change in Frankel grades, and factors that affect it were assessed by logistic regression. LOS associations were analyzed with ANOVA. RESULTS: The median age at lesion onset was 48 years, and the median survival 29 years. Age and gender had a significant effect on survival, but not so lesion severity, level, or decade of onset. Of the 69 patients who had Frankel grades A, B, or C on admission, 72% achieved useful recovery to grades D or E. The severity and level of the spinal neurological lesion (SNL) had a significant effect on recovery. The mean LOS was 87 days; it was significantly affected by lesion severity and level and by the decade of admission to rehabilitation, and decreased with time. CONCLUSIONS: Patients with DHSNL who were admitted for rehabilitation have favorable survival and recovery rates compared with previously studied patients with other types of SNL. Their LOS is probably a function of medical requirements, but is decreasing with time.

Age Factors↗
PubMed2004

Rationality versus irrationality in Egyptian medicine in the pharaonic and Graeco-Roman periods.

During the Ptolemaic Period (332 BC-31 BC), many Greek medical practitioners settled in Egypt where they established an outstanding medical school and developed a distinctive rational approach to diagnosis and treatment which some scholars have regarded as a significant advance on earlier Egyptian procedures. However, Egyptian medicine itself combined both 'rational' and 'irrational' procedures, and extant ancient sources indicate that 'rationality' was not a new concept. Also, several other medical advances that modern writers have usually attributed to the Greeks can be identified in earlier Egyptian traditions. Nevertheless, the limitations of extant textual and archaeological evidence constrain the scope of studies in this area, and new information is required to carry the debate forward.

Egypt, Ancient↗
PubMed2003

Harvesting bone graft from the posterior iliac crest by less traumatic, midline approach.

Complications of the donor site after the harvest of corticocancellous bone graft from the posterior iliac crest are very common. The most common are chronic donor site pain, tenderness, and sensory disturbances. This study investigates the results of the midline, lumbar fascia splitting approach for harvesting bone graft in lower lumbar spine fusion and compares them with the classic separate incision approach. A retrospective study of 107 patients compares two groups. The first group of 56 patients (35 males and 21 females with an average age of 41.8 years) had bone graft taken by splitting the two layers of the lumbar fascia down to their attachment to the iliac crest. The second group of 51 patients (29 males and 22 females with an average age of 43.7 years) had a separate incision over the iliac crest. In the first group, 82.1% had no tenderness, 8.9% mild, 7.1% moderate, and only 1.8% severe tenderness over the donor site. In the second group, 45.1% had no tenderness, 21.6% mild, 17.6% moderate, and 15.7% severe tenderness over the donor site. Five patients of the separate incision group (9.8%) had a lump in the donor site compared with none in the "same incision" group. Sensory disturbances over the donor site were found in 5.4% of the first group and in 21.6% of the second group. Harvesting bone graft from the posterior iliac crest for lower lumbar spine fusion through a midline, fascia splitting approach was found superior to the traditional, separate incision approach.

Adult↗
PubMed2002

[Vertebroplasty: percutaneous augmentation of vertebrae].

Vertebroplasty presents a new method for fortification of structural impaired or partially collapsed vertebrae due to various pathological disorders. According to the original method published 15 years ago, acrylic bone cement is injected percutaneously into the vertebral body under local anesthesia and fluoroscopic guidance. Indications include osteoporotic fractures, benign tumors as vertebral hemangiomas or metastatic tumors affecting the spine. Reported results are good and complications are uncommon. This article reviews the new method for restoration of the collapsed vertebra and new cement materials with osteoconductive properties.

Anesthesia, Local↗
PubMed2001

Parallel cascade identification and its application to protein family prediction.

Parallel cascade identification is a method for modeling dynamic systems with possibly high order nonlinearities and lengthy memory, given only input/output data for the system gathered in an experiment. While the method was originally proposed for nonlinear system identification, two recent papers have illustrated its utility for protein family prediction. One strength of this approach is the capability of training effective parallel cascade classifiers from very little training data. Indeed, when the amount of training exemplars is limited, and when distinctions between a small number of categories suffice, parallel cascade identification can outperform some state-of-the-art techniques. Moreover, the unusual approach taken by this method enables it to be effectively combined with other techniques to significantly improve accuracy. In this paper, parallel cascade identification is first reviewed, and its use in a variety of different fields is surveyed. Then protein family prediction via this method is considered in detail, and some particularly useful applications are pointed out.

Computational Biology↗
PubMed2001

Comparison of the ocular hypotensive lipid AGN 192024 with timolol: dosing, efficacy, and safety evaluation of a novel compound for glaucoma management.

OBJECTIVE: To compare the safety and efficacy of the ocular hypotensive lipid AGN 192024 (Lumigan) with those of timolol. METHODS: A 30-day, randomized, investigator-masked, clinical trial involving 100 patients with elevated intraocular pressure (IOP). Study medications were instilled topically. Doses of 0.003%, 0.01%, or 0.03% AGN 192024 were given once daily for 3 weeks then twice daily for 1 week, and vehicle control or 0.5% timolol was given twice daily for 4 weeks. Mean change in IOP from baseline was the primary efficacy variable. Safety parameters included adverse events, hyperemia grading, laser flare meter analysis, heart rate, and blood pressure. RESULTS: Timolol and all 3 concentrations of AGN 192024 lowered IOP from baseline (P < .001). A dosage of 0.03% AGN 192024 once daily lowered IOP significantly more than timolol (P < or = .02) at every study visit except day 21 (P = .053) and provided better diurnal IOP control. Twice-daily dosing of AGN 192024 provided no clinically significant benefit over once-daily dosing. All treatment regimens were safe and well tolerated, with no clinically significant effects on heart rate or blood pressure and no between-group differences in the incidence of adverse events. The only significant ocular safety finding with AGN 192024 was a dose-related mild increase in conjunctival hyperemia. CONCLUSIONS: Of the 3 concentrations tested, 0.03% AGN 192024 once daily had the best therapeutic profile. AGN 192024 was safe and well tolerated, and it provided superior ocular hypotensive efficacy and diurnal IOP control compared with timolol in patients with ocular hypertension and glaucoma.

Adult↗
PubMed2001

Vitreous concentration of topically applied brimonidine tartrate 0.2%.

OBJECTIVE: To determine the vitreous concentration of brimonidine after topical administration of Alphagan. DESIGN: Prospective observational case series. PARTICIPANTS: Eighteen patients scheduled for elective pars plana vitrectomy. METHODS: Brimonidine tartrate, 0.2%, was topically administered twice or three times daily for 4 to 14 days preoperatively in 13 patients. Four patients served as controls, without application of brimonidine. A dry, undiluted vitrectomy specimen obtained intraoperatively was collected, frozen, and sent to an independent bioanalytical facility for quantitative determination of vitreous concentration of brimonidine using gas chromatography/mass spectrometry. MAIN OUTCOME MEASURES: The concentration of brimonidine in human vitreous. RESULTS: All patients treated with brimonidine measured above the lower limit of quantitation with a mean vitreous concentration of 185 +/- 500 nM. All patients not treated with brimonidine measured at or below the lower limit of quantitation of 0.05 nM. There was a trend toward higher concentration in patients who were either aphakic or pseudophakic compared with those that were phakic. CONCLUSIONS: Topically applied brimonidine results in vitreous levels at or above 2 nM, the concentration shown to activate alpha(2)-receptors.

Administration, Topical↗
PubMed2001

Xenopus Eya1 demarcates all neurogenic placodes as well as migrating hypaxial muscle precursors.

We cloned two isoforms of the Xenopus Eya1 orthologue. They show identical patterns of expression that closely resemble the previously described expression of XSix1, but partly differ from the expression of Eya1 in other vertebrates. XEya1 is expressed in the somites and hypaxial muscle precursors, but not in the pronephros. Moreover, all ectodermal placodes except the lens placode strongly express XEya1. At neural plate stages, ectodermal XEya1 expression starts in two domains, the anterior neural folds and a domain lateral to the neural folds. At tailbud stages, XEya1 expression continues in the adenohypophysis, all neurogenic placodes and placodally-derived structures including cranial ganglia, the otic vesicle and lateral line primordia.

Amino Acid Sequence↗
PubMed2001

Sensitivity and positive predictive values of presurgical clinical diagnosis of excised benign and malignant skin tumors: a prospective study of 835 lesions in 778 patients.

This article reports on the sensitivity and positive predictive value of clinical diagnosis of benign and malignant skin tumors by expert plastic surgeons in an Israeli clinic. Most published reports have focused on the sensitivity of clinicians' diagnoses, a general measure of the physician's skill that does not predict the rate of accuracy of a physician's diagnoses. Our study of 835 lesions in 778 patients, one of the largest Israeli series, assesses the clinical diagnosis of malignant and benign skin tumors and is one of the few that provide information on the positive predictive value, the measure that is of interest to both physicians and patients. The majority of tumors were benign (56.8 percent), 31.6 percent were malignant, and 11.6 percent were premalignant. Among the 474 benign lesions, 46 percent were nevi. The most common nevi subclass was compound nevi (53 percent), 9 percent of the nevi were dysplastic, and 5 percent were blue nevi. The most common malignant tumor was basal cell carcinoma, accounting for 78 percent of malignant tumors. Although sensitivity for clinical diagnosis of malignancy was 91.3 percent, the positive predictive value for clinical diagnosis of malignancy was 71.3 percent. The sensitivity rate for clinically diagnosing premalignant tumors was 42.3 percent, whereas the positive predictive value for these diagnoses was higher (64.1 percent). The sensitivity rate for diagnosis of all benign lesions was 85.9 percent, and the positive predictive value was 94.2 percent. The sensitivity rate for diagnosis of all nevi was 87.6 percent, and the positive predictive value was 85.7 percent: i.e., only seven of the 218 pathologically proven diagnoses of nevi (3.2 percent) were falsely diagnosed as malignant lesions. Even more interestingly, five of the 223 clinical diagnoses of nevi (2.2 percent) were pathologically proven to be malignant melanomas, and seven were found to be premalignant lesions (3.1 percent). It was concluded that publications which report only on the sensitivity neglect to provide information of interest regarding the positive predictive value. Often, positive predictive value is qualitatively different from the sensitivity, and thus relying only on the sensitivity may lead to incorrect evaluation of a clinical judgment, which may result in erroneous surgical decisions.

Adolescent↗
PubMed2001

Xenopus cadherin-11 restrains cranial neural crest migration and influences neural crest specification.

Cranial neural crest (CNC) cells migrate extensively, typically in a pattern of cell streams. In Xenopus, these cells express the adhesion molecule Xcadherin-11 (Xcad-11) as they begin to emigrate from the neural fold. In order to study the function of this molecule, we have overexpressed wild-type Xcad-11 as well as Xcad-11 mutants with cytoplasmic (deltacXcad-11) or extracellular (deltaeXcad-11) deletions. Green fluorescent protein (GFP) was used to mark injected cells. We then transplanted parts of the fluorescent CNC at the premigratory stage into non-injected host embryos. This altered not only migration, but also the expression of neural crest markers. Migration of transplanted cranial neural crest cells was blocked when full-length Xcad-11 or its mutant lacking the beta-catenin-binding site (deltacXcad-11) was overexpressed. In addition, the expression of neural crest markers (AP-2, Snail and twist) diminished within the first four hours after grafting, and disappeared completely after 18 hours. Instead, these grafts expressed neural markers (2G9, nrp-I and N-Tubulin). Beta-catenin co-expression, heterotopic transplantation of CNC cells into the pharyngeal pouch area or both in combination failed to prevent neural differentiation of the grafts. By contrast, deltaeXcad-11 overexpression resulted in premature emigration of cells from the transplants. The AP-2 and Snail patterns remained unaffected in these migrating grafts, while twist expression was strongly reduced. Co-expression of deltaeXcad-11 and beta-catenin was able to rescue the loss of twist expression, indicating that Wnt/beta-catenin signalling is required to maintain twist expression during migration. These results show that migration is a prerequisite for neural crest differentiation. Endogenous Xcad-11 delays CNC migration. Xcad-11 expression must, however, be balanced, as overexpression prevents migration and leads to neural marker expression. Although Wnt/beta-catenin signalling is required to sustain twist expression during migration, it is not sufficient to block neural differentiation in non-migrating grafts.

Animals↗
PubMed2001

Arthrodesis with the Ilizarov device after failed knee arthroplasty.

Thirteen patients with failed total knee arthroplasty (TKA) due to infection (12 patients) or aseptic loosening (1 patient) underwent arthrodesis using the Ilizarov external fixator. Solid fusion was achieved in all patients with an average healing time of 27.6 weeks. Patients spent an average 18.8 weeks in the fixator followed by an average 8.8 weeks in a plaster cylinder cast. Five patients had a pin tract infection and one a superficial wound infection. One patient had 15 degrees recurvatum after surgery that was gradually corrected by adding a hinge system to the fixator. Average shortening of the affected limb was 3.7 cm (range: 1-6 cm). The Ilizarov fixator for knee arthrodesis after failed TKA produced favorable results and should be considered for use by surgeons familiar with the technique.

Aged↗
PubMed2001

PCR-based RNA probes: a quick and sensitive method to improve whole mount embryo in situ hybridizations.

We have developed a PCR-based technique for the preparation of RNA probes that can be used for whole mount in situ hybridization on embryos. T3 or T7 RNA polymerase promoters were introduced at the 5' end of gene-specific oligonucleotide primers enabling direct in vitro transcription of purified PCR fragments. We show for various marker genes in Xenopus embryos that this method provides equivalent results as compared to conventional vector-based probe preparation, even when fluorescence detection (FISH) is applied. This method offers a rapid and useful means to prepare gene-specific in situ probes predominantly for expression screens or detection of splice variants that previously required time-consuming cloning steps.

Animals↗