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Biomedical subjects

M Jacobs

Publications and source records attributed to M Jacobs.

At least 109 records · Page 6Linked to original sources
PubMed1996

MRI of spinal cord radiation necrosis simulating recurrent cervical cord astrocytoma and syringomyelia.

BACKGROUND: Although primary intramedullary tumors of the spinal cord with syrinx formation are well documented, there have been no reports of extensive syrinx formation or cystic degeneration associated with radiation necrosis. METHODS: We report a case of radiation necrosis and syrinx formation in a 49-year-old woman with a 5-year history of astrocytoma grade II of the cervical cord, who progressed to quadriparesis following surgery and radiation therapy. Magnetic resonance imaging (MRI) of the cervical and thoracic spine demonstrated enlargement of upper cervical cord (C1-C6) with diffuse increased signal enhancing mass by gadolinium, as well as appearance of syrinx from T4-T10. RESULTS: Autopsy findings indeed revealed a small, residual, infiltrating glioma in the upper cervical areas, but the diffuse parenchymal abnormality seen on MRI as prolonged T2 characteristics on double-echo spin-echo sequence was revealed to be radiation necrosis. CONCLUSION: What appeared to be a cystic cavity or syrinx at the thoracic level was also diagnosed as radiation necrosis with cyst formation on histologic examination.

Adult↗
PubMed1996

Oxidized low-density lipoproteins inhibit endothelium-dependent relaxations in isolated large and small rabbit coronary arteries.

1. Previous studies suggest that oxidatively modified low-density lipoproteins (oxLDL) contribute to the impairment of endothelium-dependent vasodilation in the large arteries of hypercholesterolaemic animals, whereas this may not be the case with regard to the impairment of coronary resistance vessels. For this reason, the effect of lipoproteins on coronary resistance arteries has been examined in this study. 2. The influence of lipoproteins on endothelium-dependent relaxation induced by acetylcholine (ACh) or sodium nitroprusside in PGF2 alpha-preconstricted rings from the large (1st order branch) and small coronary arteries (3rd order branch) and the aorta of New Zealand White rabbits, was investigated. 3. The sensitivity to ACh was greater in the large compared with the small diameter coronary arteries. 4. Endothelium-dependent relaxations were unaffected by native LDL. Oxidized LDL (0.5 and 1 mg protein mL-1) caused a reversible inhibition of relaxations in both preconstricted small and large coronary arteries which was overcome at high ACh concentrations. Similar inhibitions were found in the aorta. 5. Endothelium-independent relaxations elicited by sodium nitroprusside in the large and small coronary arteries were unaffected by the oxidized lipoproteins, indicating that soluble guanylate cyclase activity was unaltered. 6. It is concluded that inhibition of endothelium-dependent relaxation in the small diameter coronary arteries in hypercholesterolaemia may arise from products of oxidative modification of LDL present in the artery itself or released upstream from proximal lesions.

Acetylcholine↗
PubMed1996

Randomized phase III trial of liposomal daunorubicin versus doxorubicin, bleomycin, and vincristine in AIDS-related Kaposi's sarcoma.

PURPOSE: To compare the safety and efficacy of liposomal daunorubicin (DaunoXome; NeXstar Pharmaceuticals, Inc, Boulder, CO) with a reference regimen of doxorubicin, bleomycin, and vincristine (ABV) in advanced AIDS-related Kaposi's sarcoma (KS). PATIENTS AND METHODS: In a prospective randomized phase III trial, 232 patients were randomized to receive DaunoXome 40 mg/m2 or a combination regimen of doxorubicin 10 mg/m2, bleomycin 15 U, and vincristine 1 mg, administered intravenously every 2 weeks. Treatment was continued until complete response (CR), disease progression, or unacceptable toxicity. RESULTS: Of 232 patients randomized, 227 were treated: 116 with DaunoXome and 111 with ABV. The overall response rate (CR or partial response [PR]) was 25% (three CRs and 26 PRs) for DaunoXome and 28% (one CR and 30 PRs) for ABV. The difference in response rates was not statistically significant. The median survival time was 369 days for DaunoXome patients and 342 days for ABV patients (P = .19). The median time to treatment failure was 115 days for DaunoXome and 99 days for ABV (P = .13). ABV patients experienced significantly more alopecia and neuropathy (P < .0001). DaunoXome patients experienced more grade 4 neutropenia (P = .021). Cardiac function remained stable, with no instances of congestive heart failure on either treatment arm. CONCLUSION: In this large phase III trial, the efficacy of DaunoXome was comparable to that of ABV. Response rates, time to treatment failure, and overall survival were similar on both treatment arms. DaunoXome is a safe and effective primary therapy for advanced AIDS-related KS.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Developing a networking strategy for an integrated healthcare delivery system.

Dramatic changes in the healthcare industry are forcing organizations to find innovative ways to survive. The most critical component for organizational survival is the ability to communicate with and connect to internal and external information sources. It becomes imperative that organizations employ minimum standards and protocols in network design even as legacy systems remain in place as a part of their networks.

Computer Communication Networks↗
PubMed1996

Pharmacology of liposomal daunorubicin and its use in Kaposi's sarcoma.

In the early 1980s, we first began to see cases of Kaposi's sarcoma (KS) in patients with the lymphadenopathy now known to be associated with infection by the human immunodeficiency virus (HIV). During that period, we were still looking at strong combinations of chemotherapeutic drugs to combat this disease, based on experience in nonimmunosuppressed African patients. It rapidly became apparent, however, that we needed both better regimens and more efficient ways of targeting antineoplastic agents to tumors, because these older regimens were highly toxic. This is a common problem throughout oncology but is particularly troublesome in the treatment of patients with the acquired immunodeficiency syndrome (AIDS).

Antibiotics, Antineoplastic↗
PubMed1996

Mseleni joint disease--a molecular genetic approach to defining the aetiology.

Mseleni joint disease (MJD) is an unusual form of progressive and widespread degenerative osteoarthropathy that has been identified in several hundred people in the remote Mseleni region of northern Zululand. Affected individuals experience articular discomfort in childhood and may be seriously handicapped as adults, often requiring prosthetic hip joint replacement. Although the condition clusters in families, there is no evidence of Mendelian inheritance and assessment of affected kindreds has not shown any evidence of genomic imprinting. To date our molecular work-up has entailed the study of 47 affected individuals from MJD kindreds to investigate familial predisposition based on the inheritance of a subset of markers and/or genes on the human genome, particularly those associated with the cartilage matrix. In addition, we have collected blood specimens form 111 unaffected but unrelated individuals from the same population group in order to determine whether any relationship exists between genetic components of the human leucocyte antigen (HLA) system and the MJD phenotype. Our investigations show the following: (i) there is no association between MJD and the HLA system which has previously been associated with non-Mendelian genetic conditions; (ii) COL2A1, which has been implicated in some forms of spondylo-epiphyseal dysplasia, may be involved in at least a subset of MJD patients; and (iii) type VI collagen is overabundant in degenerated hip joint cartilage.

Black People↗
PubMed1995

Flow sorting of the Y sex chromosome in the dioecious plant Melandrium album.

The preparation of stable chromosome suspensions and flow cytometric sorting of both the Y sex chromosome of the white campion, Melandrium album, and the deleted Y chromosome of an asexual mutant, 5K63, is described. The principle has been to maintain transformed roots in vitro, synchronise and block mitosis, reduce cells to protoplasts, and lyse these to release chromosomes. Such in vitro material, unlike many cell suspensions, showed a stable karyotype. Factors critical to producing high-quality chromosome suspensions from protoplasts include osmolality of isolation solutions and choice of spindle toxin and of lysis buffer. Agrobacterium rhizogenes transformed young growing root cultures were synchronised at G1/S with 50 microM aphidicolin for 24 h and released to a mitotic block with 30 microM oryzalin for 11 h. Protoplast preparations from such tissue routinely had metaphase indices reaching 15%. Suspensions of intact metaphase chromosomes, with few chromatids, were obtained by lysing swollen mitotic protoplasts in a citric acid/disodium phosphate buffer. Except for the presence of clumps of autosomal chromosomes near the X and Y chromosome zones, monoparametric histograms of fluorescence intensities of suspensions stained with 4',6-diamino-2-phenylindole showed profiles similar to theoretical flow karyotypes. Two types of Y chromosomes, one full-length and one partially deleted (from the asexual mutant), could be sorted at 90% purity (21-fold enrichment of Y). These results are discussed in the context of sex determination and differentiation in higher plants.

Cell Line, Transformed↗
PubMed1995

Loin pain hematuria syndrome: pain relief with intrathecal morphine.

Loin pain hematuria syndrome (LPHS) is characterized by hematuria and incapacitating loin pain. The pain experienced with LPHS is, in general, extremely difficult to treat. Many surgical and pharmacologic therapies have been directed at LPHS pain without success. This report documents successful pain control in a patient with LPHS using long-term intrathecal morphine delivered via an implantable pump. Intrathecal narcotic therapy may provide pain relief for the chronic pain of LPHS.

Adult↗
PubMed1995

RITA--registry of industrial toxicology animal-data--guides for organ sampling and trimming procedures in rats.

RITA (Registry of Industrial Toxicology Animal-data) is a pathology data base for the collection of validated histopathological data on tumours and potentially pre-neoplastic lesions observed in laboratory rodents. To enable a better comparison of information, standardized techniques for the preparation of histological slides have been established for all organs. The current paper describes the guidelines for organ sampling and trimming procedures applied in the RITA project, i.e. the number of sections to be taken, the direction in which an organ should be cut, the localization (anatomical site) from which a sample should be taken, and the size of an organ (or part of an organ) to be placed in cassettes for processing. Schematical illustrations and additional explanations are provided to support the proposed standardized procedures in histology laboratories.

Animals↗
PubMed1995

A dinucleotide mutation in dihydrodipicolinate synthase of Nicotiana sylvestris leads to lysine overproduction.

By applying a mutagenesis/selection procedure to obtain resistance to a lysine analog, S-(2-aminoethyl)L-cysteine (AEC), a lysine overproducing mutant in Nicotiana sylvestris was isolated. Amino acid analyses performed throughout plant development and of different organs of the N. sylvestris RAEC-1 mutant, revealed a developmental-dependent accumulation of free lysine. Lysine biosynthesis in the RAEC-1 mutant was enhanced due to a lysine feedback-desensitized dihydrodipicolinate synthase (DHDPS). Several molecular approaches were undertaken to identify the nucleotide change in the dhdps-r1 gene, the mutated gene coding for the lysine-desensitized enzyme. The enzyme was purified from wild-type plants for amino end microsequencing and 10 amino acids were identified. Using dicotyledon dhdps probes, a genomic fragment was cloned from an enriched library of DNA from the homozygote RAEC-1 mutant plant. A dhdps cDNA, putatively full-length, was isolated from a tobacco cDNA library. Nucleotide sequence analyses confirmed the presence of the previously identified amino end preceded by a chloroplast transit peptide sequence. Nucleotide sequence comparisons, enzymatic and immunological analyses revealed that the tobacco cDNA corresponds to a normal type of DHDPS, lysine feedback-regulated, and the genomic fragment to the mutated DHDPS, insensitive to lysine inhibition. Functional complementation of a DHDPS-deficient Escherichia coli strain was used as an expression system. Reconstruction between the cDNA and genomic fragment led to the production of a cDNA producing an insensitive form of DHDPS. Amino acid sequence comparisons pointed out, at position 104 from the first amino acid of the mature protein, the substitution of Asn to Ileu which corresponds to a dinucleotide mutation. This change is unique to the dhdps-r1 gene when compared with the wild-type sequence. The identification of the nucleotide and amino acid change of the lysine-desensitized DHDPS from RAEC-1 plant opens new perspectives for the improvement of the nutritional value of crops and possibly to develop a new plant selectable marker.

Amino Acid Sequence↗
PubMed1995

A model to predict the histopathology of human stroke using diffusion and T2-weighted magnetic resonance imaging.

BACKGROUND AND PURPOSE: We sought to identify MRI measures that have high probability in a short acquisition time to predict, at early time points after onset of ischemia, the eventual development of cerebral infarction in clinical patients who suffer occlusion of a cerebral artery. METHODS: We developed an MR tissue signature model based on experimentally derived relationships of the apparent diffusion coefficient of water (ADCw) and T2 to ischemic brain tissue histopathology. In eight stroke patients we measured ADCw and T2 intensity using diffusion-weighted echo-planar imaging (DW-EPI). Tissue signature regions were defined, and theme maps of the ischemic focus at subacute time points after stroke onset were generated. RESULTS: Five MR signatures were identified in human stroke foci: two that may predict either cell recovery or progression to necrosis, one that may mark the transition to cell necrosis, and two that may be markers of established cell necrosis. CONCLUSIONS: An MR tissue signature model of ischemic histopathology using ADCw and T2 can now be tested for its potential to predict reversible and identify irreversible cellular damage in human ischemic brain regions.

Aged↗
PubMed1995

Substance use among schizophrenic outpatients: prevalence, course, and relation to functional status.

The prevalence and course of alcohol and drug use were examined in a longitudinal, retrospective study of 100 schizophrenic outpatients. During the 18 month study period, problem substance use (abuse and dependence) was not associated with differential attrition from outpatient treatment. Thirty to forty percent of subjects were using drugs or alcohol during any evaluation period. The overall level of substance use and problem use of alcohol, marijuana, and other drugs remained stable, while problem use of cocaine and multiple substances increased over time. Problem substance use was associated with lower functional status and the detrimental effect of problem substance use appeared to increase with time. These findings underscore the need to address substance use problems in the context of outpatient schizophrenia treatment.

Adult↗
PubMed1995

Combined modalities in the treatment of head and neck cancers.

The higher the T and N stages at diagnosis of head and neck cancer, the lower the proportion of patients who achieve complete, durable local control and the lower the survival. These cancers and their treatments often produce considerable anatomic distortion, affecting function, nutritional status, and appearance. New treatment approaches for locally and regionally advanced head and neck cancers are thus needed to improve survival, quality of life, or both. Combined-modality approaches show promise. Induction chemotherapy and subsequent radiotherapy produce results equivalent to aggressive surgery but allow for better organ function and speech. Induction chemotherapy and radiotherapy are superior to radiotherapy alone. Concurrent chemotherapy and radiotherapy may produce additive or synergistic interactions but increase toxicities. Some studies suggest that concurrent chemotherapy and radiotherapy significantly improves survival over radiotherapy alone in regionally advanced disease. Drug selection criteria have included enhancement of radiation cytotoxicity, effect on cellular kinetics, and, possibly, single-agent antitumor activity. The platinum compounds are of interest, especially in combination with other chemotherapy agents, like 5-fluorouracil and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ). Concurrent carboplatin and radiotherapy produced a 77-week duration of survival in responders in a University of Maryland Cancer Center study. A study of concurrent carboplatin/bleomycin/radiotherapy had to be halted because of severe bleomycin-induced mucositis. The results in this small group suggest that attenuating mucositis would be desirable. In a subsequent trial, paclitaxel, which shows considerable activity against head and neck cancers, was substituted for bleomycin. Data from the seven patients accrued thus far are too immature to define response. The study continues to accrue patients.

Antineoplastic Combined Chemotherapy Protocols↗