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Biomedical subjects

A Cohen

Publications and source records attributed to A Cohen.

At least 199 records · Page 11Linked to original sources
PubMed1999

New look at myocardial infarction: toward a better aspirin.

The evidence for the formation of NO and of its oxidation products, as well as of prostacyclin and thromboxane by the infarcted heart muscle is reviewed. The importance of inflammatory cells, primarily macrophages of cardiac origin is documented. Because of its side effects on gastric mucosa and kidney by aspirin, several modifications of aspirin are currently being developed. These are based on eliminating their inflammatory effect by selective inhibition of COX-2, or by attaching an NO-delivering side chain to the aspirin molecule (NO-aspirin), or by combining two preparations, an NO donor with aspirin. NO-aspirins and the combination of an NO-donor with aspirin promise to be beneficial in the early stages of myocardial infarction. Unfortunately, the main beneficial effect of aspirin, that of inhibition of thrombus formation, is also the cause for its most dreaded complication, hemorrhagic stroke. None of the new aspirins is able to prevent this complication.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

Intrapartum uterine rupture and dehiscence in patients with prior lower uterine segment vertical and transverse incisions.

OBJECTIVE: To determine whether gravidas with prior low vertical uterine incision(s) are at a higher risk for uterine rupture during a trial of labor after cesarean delivery than women with prior low transverse uterine incision(s). METHODS: The medical records of women undergoing a trial of labor after prior cesarean delivery over a 12-year period (July 1984-June 1996) at a tertiary-care hospital were reviewed. Maternal and perinatal outcomes for women with prior low transverse and low vertical incision were compared. Women whose low vertical incision was noted to extend into the corpus of the uterus were excluded. All uterine scar disruptions, which included both symptomatic ruptures and detected asymptomatic dehiscences, were analyzed together, and ruptures were examined separately. RESULTS: The outcomes of 2912 patients undergoing trial of labor for the low transverse group and 377 patients undergoing trial of labor for the low vertical group were compared. Overall, there were 38 (1.3%) scar disruptions in the low transverse group and six (1.6%) in the low vertical group, P = .6. There were 28 (1.0%) symptomatic ruptures in the low transverse group and 3 (0.8%) in the low vertical group, P > .999. The study had a power of 80% to detect an increase in the low vertical rupture rate from 1% (as noted for low transverse incisions) to 3%. CONCLUSION: Gravidas with a prior low vertical uterine incision are not at increased risk for uterine rupture during a trial of labor compared with women with a prior low transverse uterine incision.

Adult↗
PubMed1999

A new form of Filgrastim with sustained duration in vivo and enhanced ability to mobilize PBPC in both mice and humans.

Granulocyte colony-stimulating factor (G-CSF) has proven effective in the prophylaxis of chemotherapy-induced neutropenia and as a mobilizer of peripheral blood progenitor cells. The longevity of G-CSF action is limited by its removal from the body by two mechanisms. The first is thought to be mediated via receptors (receptor mediated clearance [RMC]) predominantly on neutrophils, the second process is likely the result of renal clearance. With the intention of developing a novel form of Filgrastim (r-met HuG-CSF) with a sustained duration of action in vivo, a new derivative named SD/01 has been made by association of Filgrastim with poly(ethylene glycol). The desired properties of this new agent would include a prolonged duration of action sufficient to cover a complete single course of chemotherapy. SD/01 is shown here to sustain significantly elevated neutrophil counts in hematopoietically normal mice for 5 days. In neutropenic mice effects were noted for at least 9 days, accompanying a significant reduction in the duration of chemotherapy induced neutropenia. Normal human volunteers showed higher than baseline ANC for around 9 to 10 days after a single injection of SD/01. Data from these normal volunteers also indicate that mobilization of CD34+ cells and progenitors may occur in a more timely manner and to around the same absolute numbers as with repeated daily injections of unmodified Filgrastim. These data indicate that SD/01 represents an efficacious novel form of Filgrastim with actions sustained for between one and two weeks from a single injection.

Animals↗
PubMed1999

Nutritional status and growth after bone marrow transplantation (BMT) during childhood: EBMT Late-Effects Working Party retrospective data. European Group for Blood and Marrow Transplantation.

The European Group for Blood and Marrow Transplantation (EBMT) Late-Effects Working Party collected data on patients who survived more than 5 years after BMT. Height at transplant and at the latest follow-up examination were evaluated in 79/258 subjects who were below the age of 15 at BMT. A significant decrease in height-standard deviation score (SDS) was observed in leukemic children conditioned with total body irradiation (TBI) and in those who received both cranial irradiation and TBI. The majority of these patients, however, received single-dose TBI (28/41). A significant decrease in height-SDS was also seen in children who received thoraco-abdominal irradiation suggesting that the deleterious effect of irradiation on growth after BMT is not entirely due to injury to cranial neuroendocrine structures, but also probably due to damage to bone epiphyses, thyroid and gonads. A non-significant decrease in height was observed in children transplanted using chemotherapy alone. Nutritional status, expressed as body-mass index (BMI), was found unchanged in the adult group (n = 158). A significant increase in BMI was observed in the younger patients (n = 88), which parallels the normal increase in BMI observed during childhood. This suggests that on long-term analysis, a good nutritional status is maintained in patients undergoing BMT at any age.

Adolescent↗
PubMed1999

Relapse of cutaneous leishmaniasis in a patient with an infected subcutaneous rheumatoid nodule.

Cutaneous leishmaniasis is a protozoal infection generally considered to be limited to the skin. In Israel, the disease is common in geographically defined areas and is caused predominantly by Leishmania major. Sporotrichoid subcutaneous spread has been reported but is uncommon. We describe a patient with rheumatoid arthritis, treated with methotrexate and prednisone, in whom numerous rheumatoid nodules concomitant with cutaneous leishmaniasis were found, mimicking sporotrichoid spread of the disease. In a rheumatoid nodule that was examined by electron microscopy, Leishmania parasites were found at intracellular and extracellular locations. This observation supports the hypothesis that cutaneous leishmaniasis parasites persist after clinical cure of the disease and may re-emerge as a result of immunosuppression.

Humans↗
PubMed1999

The value of histomorphometric nuclear parameters in the diagnosis of well differentiated follicular carcinomas and follicular adenomas of the thyroid gland.

AIMS: To explore the potential of histomorphometric analysis in distinction between follicular adenomas and well differentiated follicular carcinomas of the thyroid gland. Their differentiation on routine histological study may be a challenging exercise, being contingent upon the absence or presence of vascular invasion and penetration of neoplastic follicles through the capsule of the tumour. METHODS AND RESULTS: Computer-assisted image analysis was performed to gauge the nuclear area, nuclear Ferret diameter, nuclear regularity factor, nuclear elongation factor, number of nuclear vesicles and total area of all nuclear vesicles in the follicles of 37 adenomas and 36 well differentiated carcinomas. By univariate analysis, these nuclear descriptors (with the exception of the elongation factor) were found to correlate with the benign or malignant nature of the tumours. By multivariate analysis, only the nuclear area, Ferret diameter and regularity factor were ascertained to be significant predictors of malignancy. A fitted logit model correctly predicted 91% of the cancers and 87% of the adenomas. CONCLUSIONS: Histomorphometrically gauged nuclear parameters of the tumour cells may reinforce pathologists' decision-making by adding objective and unbiased criteria to their subjective assessment of follicular neoplasms in cases in which vascular or capsular invasion are not detected.

Adenocarcinoma, Follicular↗
PubMed1999

Nulliparas' preferences for epidural analgesia: their effects on actual use in labor.

BACKGROUND: Few studies have directly examined the reasons for choices of pain relief during labor. The purpose of this study was to investigate if women's preferences for epidural analgesia in labor have an impact on the use of intrapartum epidural analgesia. METHODS: Nulliparous women attending childbirth classes completed questionnaires about their antenatal preferences for the use of intrapartum epidural analgesia. Data on actual use of analgesia was obtained by chart review. The analysis included 303 women with either spontaneous or induced labor at term. RESULTS: The 185 women who planned to receive epidural analgesia had a markedly higher rate of epidural use (91%) than the 110 women who hoped to avoid it (57%) (p = 0.001). Of 237 epidurals administered, 169 (71%) were planned during the antenatal period. Among women receiving epidural analgesia, those planning to receive it tended to have more frequent early administration (< or = 3 cm cervical dilation) than women who unsuccessfully tried to avoid epidural use (54% vs. 24%, p = 0.003). CONCLUSION: In our population of nulliparas, a woman's antenatal plan to receive epidural analgesia is strongly associated with her likelihood of receiving it. Women who plan to receive epidural analgesia have earlier administration.

Adult↗
PubMed1999

Unusual complication of ligation of rudimentary ulnar digit.

We report a case of rudimentary ulnar polydactyly of the hand of a 7-year-old female child. Histological examination revealed a central traumatic neuroma which branched into five digit-like projections covered with hyperkeratotic epidermis. We think this was a result of suture ligation during the postnatal period.

Child↗
PubMed1999

Self heat-shock protein (hsp60) peptide serves in a conjugate vaccine against a lethal pneumococcal infection.

Healthy persons manifest a high frequency of T cells reactive to epitopes of the self 60-kDa heat-shock protein (hsp60) molecule. It was reasoned that a self hsp60 peptide, p458m, might provide T cell help for a response to the T independent capsular polysaccharide of Streptococcus pneumoniae type 4 (PS4). The conjugate vaccine (PS4-p458m) induced resistance to challenge with >300,000 times the minimal lethal dose of pneumococci. PS4 conjugated to other immunogenic carriers (tetanus toxoid, a pneumolysin peptide, and others) or a commercial pneumococcal vaccine were far less effective. The effectiveness of the PS4-p458m conjugate was associated with an increased IgG1 antibody response to PS4, with long-term memory, and with T cell responses to the p458m peptide. Thus, T cell reactivity to a self epitope in a conjugate vaccine can be mobilized to induce help for resistance to a lethal infection.

Animals↗
PubMed1999

Position effect variegation at the mating-type locus of fission yeast: a cis-acting element inhibits covariegated expression of genes in the silent and expressed domains.

Schizosaccharomyces pombe switches its mating type by transposing a copy of unexpressed genes from the respective mat2 or mat3 cassettes to mat1. The donor cassettes are located in a silent domain that is separated from the expressed mat1 cassette by the L region. We monitored the expression of ade6 from sites in the L region and examined the relationship between the expression state at these sites and at sites within the silent domain. Results indicate that: (1) the silent domain extends into the L region, but repression is gradually alleviated with increasing distance from mat2, and overexpression of swi6 enhances PEV in the L region; (2) a transcriptionally active chromatin state, associated with reporter gene expression in the L region, spreads toward the silent domain; (3) a cis-acting element, located at the junction between the L region and mat2-P, ensures repression in the silent domain, regardless of the expression state in the L region; and (4) repression in mat1-P cells is less stringently controlled than in mat1-M cells. We discuss the functional organization of the mat region and genetic elements that ensure separation between repressed and derepressed domains.

Adenine↗
PubMed1999

Early outcome and complications of the extended subcranial approach to the anterior skull base.

OBJECTIVES: To present the technique of the extended subcranial approach to the anterior skull base and to review the results in 55 patients who underwent the procedure. STUDY DESIGN: Retrospective review of the records of 55 patients who underwent the extended subcranial approach to the anterior skull base between 1994 and 1998 for the treatment of various neoplasms originating in the nasal cavity, nasopharynx, paranasal sinuses, orbit, or meninges, as well as for the repair of complex craniofacial trauma and/or cerebrospinal fluid (CSF) leak. Preoperative patient evaluation and the surgical technique are also reviewed. METHODS: Patient records were retrospectively reviewed and tabulated for age, sex, and indications for procedure, with special focus on early outcome and complications. RESULTS: Twenty-six patients underwent oncologic resections, 22 patients had reduction of complex fronto-naso-orbital and skull base fractures, and seven patients had repair of CSF leak. Significant complications in the oncologic group consisted of one hematoma requiring needle aspiration and two cases of temporary nontension pneumocephalus. In the fracture group, one patient died because of extensive intracerebral damage and multiorgan failure, and one patient had nontension pneumocephalus coupled with CSF leakage and one patient had temporary nontension pneumocephalus. The most common late complication in all three groups was anosmia. CONCLUSIONS: Based on their review, the authors conclude that the extended subcranial approach to the anterior skull base is a safe, versatile, and effective procedure for the surgical treatment of various pathological conditions involving the anterior skull base.

Adolescent↗
PubMed1999

Alpha1-microglobulin chromophores are located to three lysine residues semiburied in the lipocalin pocket and associated with a novel lipophilic compound.

Alpha1-microglobulin (alpha1m) is an electrophoretically heterogeneous plasma protein. It belongs to the lipocalin superfamily, a group of proteins with a three-dimensional (3D) structure that forms an internal hydrophobic ligand-binding pocket. Alpha1m carries a covalently linked unidentified chromophore that gives the protein a characteristic brown color and extremely heterogeneous optical properties. Twenty-one different colored tryptic peptides corresponding to residues 88-94, 118-121, and 122-134 of human alpha1m were purified. In these peptides, the side chains of Lys92, Lys118, and Lys130 carried size heterogeneous, covalently attached, unidentified chromophores with molecular masses between 122 and 282 atomic mass units (amu). In addition, a previously unknown uncolored lipophilic 282 amu compound was found strongly, but noncovalently associated with the colored peptides. Uncolored tryptic peptides containing the same Lys residues were also purified. These peptides did not carry any additional mass (i.e., chromophore) suggesting that only a fraction of the Lys92, Lys118, and Lys130 are modified. The results can explain the size, charge, and optical heterogeneity of alpha1m. A 3D model of alpha1m, based on the structure of rat epididymal retinoic acid-binding protein (ERABP), suggests that Lys92, Lys118, and Lys130 are semiburied near the entrance of the lipocalin pocket. This was supported by the fluorescence spectra of alpha1m under native and denatured conditions, which indicated that the chromophores are buried, or semiburied, in the interior of the protein. In human plasma, approximately 50% of alpha1m is complex bound to IgA. Only the free alpha1m carried colored groups, whereas alpha1m linked to IgA was uncolored.

Animals↗
PubMed1999

A RecG-independent nonconservative branch migration mechanism in Escherichia coli recombination.

To gain insight regarding the mechanisms that extend heteroduplex joints in Escherichia coli recombination, we investigated the effect of recG and ruv genotypes on heteroduplex strand polarity in intramolecular recombination products. We also examined the cumulative effect of mutational inactivation of RecG and single-strand-specific exonucleases on recombination proficiency and the role of Chi sites in RecG-independent recombination. All four strands of the two homologs were incorporated into heteroduplex structures in wild-type cells and in ruv mutants. However, in recG mutants heteroduplexes were generated almost exclusively by pairing the invasive 3'-ending strand with its complementary strand. To explain the dependence of strand exchange reciprocity on RecG activity, we propose that alternative mechanisms may extend the heteroduplex joints after homologous pairing: a reciprocal RecG-mediated mechanism and a nonreciprocal mechanism, mediated by RecA and single-strand-specific exonucleases. The cumulative effect of recG and recJ or xonA mutations on recombination proficiency and the inhibitory effect of recJ and xonA activities on heteroduplex formation by the 5'-ending strands are consistent with this proposal.

Bacterial Proteins↗
PubMed1999

Pharmacokinetics and tolerability of intravenous trecovirsen (GEM 91), an antisense phosphorothioate oligonucleotide, in HIV-positive subjects.

Trecovirsen, a 25-mer antisense phosphorothioate oligonucleotide targeted at the gag site of the HIV gene, was administered to HIV-positive volunteers as an i.v. infusion. Single doses ranged from 0.1 to 2.5 mg/kg in an ascending escalation in cohorts of 6 to 12 subjects. Plasma trecovirsen concentrations and pharmacokinetic parameters could be assessed at doses > or = 0.3 mg/kg. Peak plasma concentrations and AUC values increased disproportionately with increasing dose while elimination half-life increased and plasma clearance decreased, indicating a saturable process over this dose range. The only significant adverse event observed was an isolated, transitory increase in activated partial thromboplastin time at doses > or = 2.0 mg/kg that was related to plasma trecovirsen concentrations and is attributed to the polyanionic character of the molecule. Thus, trecovirsen administration was well tolerated in single i.v. doses up to 2.5 mg/kg.

Adult↗