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Biomedical subjects

A Jacobs

Publications and source records attributed to A Jacobs.

At least 55 records · Page 3Linked to original sources
PubMed2000

Relative sparing of the parietal cortex in cerebellar ataxia documented by positron emission tomography.

With the intention to assess remote effects of cerebellar dysfunction, 23 patients with inherited or idiopathic cerebellar ataxia were studied with positron emission tomography (PET) and 2[18F]fluoro-2-deoxy-D-glucose (FDG). Eight patients (group 1) suffered from early onset cerebellar ataxia (EOCA, age of symptom onset <20 years), nine patients (group 2) from late onset cerebellar ataxia (LOCA, symptom onset between the ages of 20 and 50), and six patients (group 3) experienced symptom onset beyond the age of 50 years. The pattern of cerebral glucose metabolism in cerebellar ataxia was compared to the results in a control group of 16 healthy subjects. In all patients, a reduction in relative (EOCA, group 1) or absolute (LOCA, groups 2 and 3) values of regional cerebral glucose metabolism (rCMR(glu)) occurred in both cerebellar hemispheres as well as the vermis and both dentate nuclei. In patients from all groups presenting with a clinical syndrome of pure cerebellar ataxia, impairment of regional glucose metabolism also extended to the pontine and brainstem regions. In contrast to this infratentorial reduction of rCMR(glu) in all patients, in those with LOCA, a significant relative increase in rCMR(glu) was present in distinct supratentorial cortical regions, namely the cuneus, the pre-cuneus and the gyrus supramarginalis in the patients of group 2. In group 3, this significant relative increase in rCMR(glu) was restricted to the cuneus. Thus, FDG-PET in patients suffering from cerebellar ataxia shows distinct patterns of altered glucose metabolism which exceed pure cerebellar impairment. Most importantly, FDG-PET yields insight into the influence of cerebellar disease on supratentorial glucose metabolism and documents impairment of supratentorial neuronal function with relative sparing of the parietal cortex.

Adult↗
PubMed2000

[Value of the Susan Isernhangen Evaluation of Functional Capacity Scale in medical and occupational rehabilitation].

In Germany, Susan Isernhagen's Functional Capacity Evaluation (FCE) system has increasingly come into use over the last few years at the interface between medical and vocational rehabilitation. With implementation of these work-related tests of functional capacity it is possible to obtain valid statements concerning the further vocational prognosis. Along with evaluative testing by experts from different disciplines, the further steps towards integration occur on a well-founded basis. Therapies may thus be adjusted to the requirements of work, either at the former workplace or a new one, or possibly of a vocational (re-)training measure. Also, it is possible to directly deal with work-related issues in the report given at the end of rehabilitation, to initiate preliminary integrative steps in order to achieve a seamless, job retention-focussed transition back into work life. Work is simulated at different levels of loading capacity, the functional deficits of the rehabilitees are addressed in a specific, job-related manner, so as to enable an early return to work after rehabilitation.

Disability Evaluation↗
PubMed2000

Precision of automatic measurements of pigmented skin lesion parameters with a MelaFind(TM) multispectral digital dermoscope.

The purpose of this study was to assess the precision of automatic computerized measurement of parameters that may be useful in the differentiation of malignant melanoma from benign pigmented skin lesions, and also to determine the feasibility of quantitative monitoring of skin lesions over time. Ten independent sequences of images were acquired with a MelaFind multispectral digital dermoscope for each of 12 benign or malignant pigmented skin lesions. The sequences of images were processed automatically to provide 10 independent measurements of the various parameters for each lesion. Parameters included lesion area, greatest 'diameter', perimeter, reflectance and asymmetry. The precision of each parameter determination was computed from the mean and standard deviation of the 10 measurements of that parameter. The relative errors in determining the lesion area, 'diameter' and perimeter were found to be 6%, 3% and 4%, respectively. Other lesion parameters that are used in differentiating melanomas from benign skin lesions were also analysed as a function of wavelength. In the blue band (about 430 nm) the relative error was about 7% for the mean lesion reflectance and about 7% for the asymmetry parameter. These results demonstrate the feasibility of using MelaFind for objective quantitative monitoring of changes in pigmented skin lesions over time. As suggested by some studies, such information is useful in the early detection of malignant melanoma. The results show that parameters obtained automatically from MelaFind images are sufficiently precise to allow pertinent parameters to be used to classify pigmented skin lesions.

Databases, Factual↗
PubMed2000

Functional magnetic resonance imaging aided radiation treatment planning.

Functional MRI (magnetic resonance imaging) allows one to noninvasively identify various eloquent cortices in the brain. The integration of cortical activation information into radiosurgical treatment planning may provide an alternative to prevent or minimize radiation damage to eloquent cortex. A novel approach of directly integrating the fMRI (functional magnetic resonance imaging) brain map into treatment planning is proposed. Three brain tumor patients have been studied using this method with motor and/or visual paradigms. Brain activation was demonstrated in eloquent cortex at the precentral gyrus (motor area) and medial occipital lobe (visual area). The activation maps were transferred to a treatment planning workstation, (XKnife), and 3D (three-dimensional) activation maps were generated and co-registered to a 3D CT (computed tomography) anatomical data set, which provided the calibration localizer, for treatment planning. Radiosurgery was designed based on both functional and structural information by the medical team consisting of a radiation oncologist, a neurosurgeon and a physicist. The average maximum dose for the tumor was 2113 cGy. The average maximum dose for tissue surrounding the tumor was 1600 cGy. The average dose with fMRI information to the eloquent cortex was 163.4 cGy over three patients, while without fMRI information it was 240.5 cGy. The average percentage dose reduction over three patients is 32%. The results suggest that using this method can reduce the dose to the eloquent cortex. This approach provides the physician with additional information for treatment planning and may spare the patient unnecessary radiation exposure to adjacent eloquent cortices.

Adult↗
PubMed2000

Reductively activated cleavage of DNA mediated by o, o'-diphenylenehalonium compounds.

o,o'-Diphenylenehalonium (DPH) cations represent a novel class of DNA-affinic compounds characterized by binding constants within the range of 10(5)-10(6) M(-1). The maximum binding capacity of 2-2.5 base pairs per DPH cation and about 30% hypochromic reduction in the optical absorption of DPH cations upon binding to DNA suggest intercalation as a likely binding mode. In a DNA-bound form, DPH cations induce strand breaks upon reduction by radiation-produced electrons in aqueous solutions. In keeping with this mechanism, the cleavage is strongly inhibited by oxygen and is not affected by OH radical scavengers in the bulk. The yields of DPH-mediated base release significantly exceed the yield of base release caused by hydroxyl radical (in the absence of scavenger) in anoxic solutions. The yields are weakly dependent on DNA loading within the range from 5 to 50 base pairs per intercalator, which indicates the ability of excess electrons in DNA to react with a scavenger separated by tens of base pairs from the electron attachment site. The question regarding the mechanism by which the distant reactants reach each other in DNA remains unanswered, although it most likely involves electron hopping rather than a single-step long-distance tunneling. The latter conclusion is based on our finding that the electron affinity of DPH cations does not affect their properties as electron scavengers in DNA as would be expected if the direct long-distance tunneling is involved.

Cations↗
PubMed2000

Digital radiography versus conventional radiography in chest imaging: diagnostic performance of a large-area silicon flat-panel detector in a clinical CT-controlled study.

OBJECTIVE: The objective of this study was to compare the diagnostic performance of a digital large-area silicon flat-panel detector with that of a conventional screen-film system in clinical chest imaging using abnormal findings documented by CT as the reference standard. SUBJECTS AND METHODS: Eighty patients (46 men and 34 women; age range,18-91 years; mean age, 63 years) who underwent CT of the chest were examined with the new digital radiography system, which is based on a 43 x 43 cm silicon flat-panel detector, and with a conventional screen-film system, which is used routinely in clinical practice. Posteroanterior and lateral radiographs were obtained. Four radiologists analyzed the digital and conventional images separately for chest abnormalities and rated the images using a five-level scale of confidence; CT was used as the reference standard. Diagnostic value was assessed using receiver operating characteristic curves for each abnormality. RESULTS: No significant differences were found between the area under the receiver operating characteristic curve of the digital and that of the conventional radiography method for almost all investigated criteria. The only exception was mediastinal abnormalities, for which the digital method provided better results than the conventional method (p < 0.05). CONCLUSION: The diagnostic performance of the new large-area silicon flat-panel detector is equivalent or superior to that of the conventional screen-film system for clinical chest imaging and can replace conventional radiography systems. This new technology offers transmission and storage possibilities inherent to digital radiology that would facilitate daily practice and reduce the initial high costs in the long-term.

Adolescent↗
PubMed2000

Interferon alpha-2a and 13-cis-retinoic acid in patients with metastatic renal cell cancer.

Treatment of patients with metastatic renal cell cancer (RCC) with interferon-alpha-2a (IFN) and 13-cis-retinoic acid (CRA) was first reported to be tolerable on an outpatient basis and to yield a 30% objective response rate. We sought to confirm these preliminary results by conducting a phase II trial of therapy with IFN/CRA in patients with bidimensionally measurable RCC. Twenty-five patients were enrolled. The median age was 58 (range, 47-75 years) and the median Karnofsky performance status was 90 (range 60-100). Seventeen patients (60%) had undergone prior nephrectomy and none had received prior systemic therapy. Treatment consisted of oral CRA at 1 mg/kg/day and IFN self-administered by subcutaneous injection at 3 MU/day with weekly escalation to 6 and 9 MU/day. Treatment was well tolerated, with cheilitis, influenza-like symptoms, and fatigue the most common toxicities. Severe toxicity was reversible and consisted of grade 4 cheilitis in one patient and grade 3 malaise/fatigue in two patients. One complete and four partial responses were observed, for an objective response rate of 20% (95% confidence interval, 4-36%). We conclude that treatment with CRA/IFN for RCC is tolerable on an outpatient basis and induces objective responses in some patients. The contribution, if any, of CRA to the responses observed will be determined in ongoing randomized phase III trials.

Administration, Oral↗
PubMed1999

Caveolin-1 modulates the activity of the volume-regulated chloride channel.

1. Caveolae are small invaginations of the plasma membrane that have recently been implicated in signal transduction. In the present study, we have investigated whether caveolins, the principal protein of caveolae, also modulate volume-regulated anion channels (VRACs). 2. ICl,swell, the cell swelling-induced chloride current through VRACs, was studied in three caveolin-1-deficient cell lines: Caco-2, MCF-7 and T47D. 3. Electrophysiological measurements showed that ICl, swell was very small in these cells and that transient expression of caveolin-1 restored ICl,swell. The caveolin-1 effect was isoform specific: caveolin-1beta but not caveolin-1alpha upregulated VRACs. This correlated with a different subcellular distribution of caveolin-1alpha (perinuclear location) from caveolin-1beta (perinuclear and peripheral). 4. To explain the modulation of ICl, swell by caveolin-1 we propose that caveolin increases the availability of VRACs in the plasma membrane or, alternatively, that it plays a crucial role in the signal transduction cascade of VRACs.

Animals↗
PubMed1999

Bioimpedance: is it a predictor of true water volume?

Bioelectrical impedance analysis (BIA) has been reported to be insensitive to changes in water volumes in individual subjects. This study was designed to investigate the effect on the intra- and extracellular resistances (Ri and Re) of the segments of subjects for whom body water was changed without significant change to the total amount of electrolyte in the respective fluids. Twelve healthy adult subjects were recruited. Ri and Re of the leg, trunk, and arm of the subjects were determined from BIA measures prior to commencement of two separate studies that involved intervention, resulting in a loss/gain of body water effected either by a sauna followed by water intake (study 1) or by ingestion (study 2). Ri and Re of the segments were also determined at a number of times following these interventions. The mean change in body water, expressed as a percentage of body weight, was 0.9% in study 1 and 1.25% in study 2. For each study, the results for each subject were normalized for each limb to the initial (prestudy) value and then the normalized results for each segment were pooled for all subjects. ANOVA of these pooled results failed to demonstrate any significant differences between the normalized mean values of Ri or Re of the segments measured through the course of each study. The failure to detect a change in Ri or Re is explained in terms of the basic theory of BIA.

Analysis of Variance↗
PubMed1999

Local fish consumption and serum PCB concentrations among Mohawk men at Akwesasne.

A study was conducted to assess local fish consumption patterns and their relationship to concentrations of total polychlorinated biphenyls (PCBs) in the serum of Mohawk men residing near three hazardous waste sites. From 1992 to 1995, 139 men were interviewed and donated a 20-ml venous blood sample. The results indicated that the men ate a mean of 21.2 local fish meals during the past year, compared with annual means of 27.7 meals 1-2 years before and 88.6 meals more than 2 years before (P<0.001 for test of trend). This change is probably a consequence of advisories issued against the consumption of local fish, since 97% of the men were aware of the advisories and two-thirds had changed their behavior as a result. Multiple regression analysis revealed that serum PCB levels increased with age (beta=0.036, P<0.001) and local fish consumption (beta=0.088, P=0.006). The data suggest that local fish consumption has contributed to body burdens in this population and that the advisories have been effective in modifying local fish consumption habits.

Adolescent↗
PubMed1999

Assessing environmental exposure to PCBs among Mohawks at Akwesasne through the use of geostatistical methods.

The Mohawk Nation at Akwesasne is a Native American community located along the St. Lawrence River in New York State, Ontario, and Quebec. One component of a multiphase human health study was to assess the impact of different pathways of human exposure resulting from the off-site migration of polychlorinated biphenyl (PCB) contamination in this area. This paper illustrates how mapped residential information and environmental sampling data can be united to assist in exposure assessment for epidemiologic studies using geographic information system (GIS) technology and statistical methods. A proportional sampling scheme was developed to collect 119 surface soils. Using a method of cross validation, the average estimated error can be computed and the best estimator can be selected. Seven spatial methods were examined to estimate surface soil PCB concentrations; the lowest relative mean error was 0.42% for Inverse 3 nearest neighbor weighted according to the inverse distance, and the highest relative mean error was 4.4% for Voronoi polygons. Residual plots indicated that all methods performed well except near some of the sampling points that formed the outer boundaries of the sampling distribution.

Environmental Exposure↗
PubMed1999

Patterns of failure in endometrial carcinoma stage IB grade 3 and IC patients treated with postoperative vaginal vault brachytherapy.

OBJECTIVE: The vagina is the most common site of locoregional failure in surgical stage IB, IC, and II (occult) endometrial adenocarcinoma. The objective of this study is to evaluate the therapeutic efficacy of vaginal vault brachytherapy alone for surgical stage I patients with high-risk features. MATERIALS AND METHODS: The study group consists of high-risk stage I patients with either stage IB grade (G) 3 or any grade IC disease. From February 1991 to August 1997, 124 patients with endometrial carcinoma were treated postoperatively with high-dose-rate vaginal vault brachytherapy as the only adjuvant treatment. All patients were surgically staged. Among them, 38 patients were identified as high risk. Twelve patients had stage IBG3, 14 had ICG1, 9 had ICG2, and 3 had ICG3 disease. The median age was 67 years (range 41 to 86 years). A dose of 21 Gy in three fractions of 7 Gy each was delivered to a prescription depth of 0.5 cm from the surface of the vaginal applicator using high-dose-rate brachytherapy. RESULTS: The median follow-up was 30 months (range 7 to 91 months). No patient has developed a vaginal or pelvic recurrence. Three patients developed tumor recurrence in the upper abdomen at 11, 18, and 37 months. Two of the three patients with recurrent disease also had history of breast cancer. In one patient, breast cancer was diagnosed 4.8 years prior and in the second 3 years subsequent to the diagnosis of endometrial cancer. The 5-year actuarial overall survival and disease-free survival are 93 and 87%, respectively. There was no treatment-related grade 3 or 4 morbidity observed. CONCLUSIONS: For patients with surgical stage IBG3 and IC, excellent local control and minimal morbidity has been observed with the selective use of vaginal brachytherapy alone. Further studies and longer follow-up are warranted.

Adenocarcinoma↗
PubMed1999

Gene silencing results in instability of antibody production in transgenic plants.

The stability of antibody and Fab expression was assessed in five different homozygous transgenic Arabidopsis lines. Each of these lines showed silencing of the transgenes that encode the antibody polypeptides, leading to instability of antibody production. However, each line had a different and specific instability profile. The characteristic variation in the level of antibody accumulation in each line as a function of developmental stage indicated that the T-DNA integration pattern played a role in triggering silencing, and also that the history and the integration position of simple transgene loci can influence the susceptibility to epigenetic silencing. In different lines with low antibody accumulation levels, methylation was found either in the promoter alone, in both the promoter and the transcribed region, in the transcribed region only, or in the transcribed region and downstream sequences. In conclusion, our data suggest that epigenetic effects result in different transgene expression profiles in each of the five Arabidopsis lines analyzed.

Antibody Formation↗
PubMed1999

Improved performance of seroconversion with a 4th generation HIV antigen/antibody assay.

Recently a new fourth generation microELISA for large scale blood screening has been described in which HIV p24 Ag detection was integrated in an anti-HIV-1/-2 and anti-HIV-1 group O assay based on a direct assay format: (Vironostika HIV Uni-Form II Ag/Ab (Van Binsbergen et al., (1998)). When compared to the third generation a-HIV assay (Vironostika HIV Uni-Form II plus O), the seroconversion window was narrowed with more than one week. A more precise window estimation based on seroconversion series with short sampling time intervals of up to 7 days, is described in parallel with that for the single HIV p24 Ag assay. It was found with 10 relevant seroconversion series that the HIV p24 Ag assay closes the seroconversion window with 6.2 days as compared to the 3rd generation a-HIV assay, while a window reduction of 4 days was found with Vironostika HIV Uni-Form II Ag/Ab. These seroconversion data show that with the new assay two-thirds of the current p24 Ag window is closed. There was no statistical difference in seroconversion sensitivity between the HIV p24 Ag and the new assay format. An extended evaluation of the new assay with subtype HIV-1 M and group O p24 Ag strains and with anti-HIV antibodies obtained from individuals infected with different HIV-1 subtypes showed that all subtypes of HIV-1 M and HIV-1 group O p24 antigen were detected as well as of HIV antibody.

Enzyme-Linked Immunosorbent Assay↗
PubMed1999

Maternal care and attachment security in ordinary and emergency contexts.

One of the foundations of attachment theory is the notion that early care plays a key role in determining the quality of child-caregiver attachment relationships. Studies have consistently shown relations between maternal sensitivity and infant security. Further research is required to resolve issues arising from modest correlations, focus on research in stressful as opposed to ordinary contexts, and questions about the generality of results across cultures and social contexts and about the context specificity of caregiving behavior. This article addressed these issues in 2 studies of child care in home and hospital contexts. Q-sort scores derived from extended naturalistic observations were used. Results are discussed in terms of links between methodology and effect sizes, the generality of links between maternal care and child security, the need for further research on caregiving in ordinary and emergency situations, and the context sensitivity of maternal behavior.

Adult↗
PubMed1999

Functional coexpression of HSV-1 thymidine kinase and green fluorescent protein: implications for noninvasive imaging of transgene expression.

Current gene therapy technology is limited by the paucity of methodology for determining the location and magnitude of therapeutic transgene expression in vivo. We describe and validate a paradigm for monitoring therapeutic transgene expression by noninvasive imaging of the herpes simplex virus type 1 thymidine kinase (HSV-1-tk) marker gene expression. To test proportional coexpression of therapeutic and marker genes, a model fusion gene comprising green fluorescent protein (gfp) and HSV-1-tk genes was generated (tkgfp gene) and assessed for the functional coexpression of the gene product, TKGFP fusion protein, in rat 9L gliosarcoma, RG2 glioma, and W256 carcinoma cells. Analysis of the TKGFP protein demonstrated that it can serve as a therapeutic gene by rendering tkgfp transduced cells sensitive to ganciclovir or as a screening marker useful for identifying transduced cells by fluorescence microscopy or fluorescence-activated cell sorting (FACS). TK and GFP activities in the TKGFP fusion protein were similar to corresponding wild-type proteins and accumulation of the HSV-1-tk-specific radiolabeled substrate, 2'-fluoro-2'-deoxy-1beta-D-arabinofuranosyl-5-iodo-uracil (FIAU), in stability transduced clones correlated with gfp-fluorescence intensity over a wide range of expression levels. The tkgfp fusion gene itself may be useful in developing novel cancer gene therapy approaches. Valuable information about the efficiency of gene transfer and expression could be obtained by non-invasive imaging of tkgfp expression with FIAU and clinical imaging devices (gamma camera, positron-emission tomography [PET], single photon emission computed tomography [SPECT]), and/or direct visualization of gfp expression in situ by fluorescence microscopy or endoscopy.

Animals↗
PubMed1999

HSV-1-based vectors for gene therapy of neurological diseases and brain tumors: part I. HSV-1 structure, replication and pathogenesis.

The design of effective gene therapy strategies for brain tumors and other neurological disorders relies on the understanding of genetic and pathophysiological alterations associated with the disease, on the biological characteristics of the target tissue, and on the development of safe vectors and expression systems to achieve efficient, targeted and regulated, therapeutic gene expression. The herpes simplex virus type 1 (HSV-1) virion is one of the most efficient of all current gene transfer vehicles with regard to nuclear gene delivery in central nervous system-derived cells including brain tumors. HSV-1-related research over the past decades has provided excellent insight into the structure and function of this virus, which, in turn, facilitated the design of innovative vector systems. Here, we review aspects of HSV-1 structure, replication and pathogenesis, which are relevant for the engineering of HSV-1-based vectors.

Brain Neoplasms↗