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Biomedical subjects

M Geller

Publications and source records attributed to M Geller.

At least 19 recordsLinked to original sources
PubMed2006

Serum IgE levels in neurofibromatosis 1.

A descriptive case study was performed on 75 patients with NF1 (neurofibromatosis type 1) from the CNNF (Brazil) database. Serum IgE levels were determined using the IgE radioimmunosorbent test, with the reference values of 75-502 IU mL(-1). The patients were divided into groups, with 25 patients presenting plexiform neurofibromas, 25 presenting neurofibromas and 25 presenting no neurofibromas. The purposes of this study were to determine the serum IgE levels of patients with NF1 presenting plexiform neurofibromas, neurofibromas and no neurofibromas, as well as to determine possible correlations between serum IgE levels and the size of the plexiform neurofibromas and neurofibromas presented by these patients. Elevated serum IgE levels were observed in all the patient groups. We did not observe a correlation between IgE levels and age in these patients; however, we did observe correlations between IgE levels and neurofibroma and plexiform neurofibroma size. We suggest further studies to confirm these results and to investigate in greater depth the possible role of IgE in the development and growth of neurofibromas and plexiform neurofibromas in NF1.

Adolescent↗
PubMed2005

Angiogenesis in normal and neoplastic ovaries.

Ovarian physiology is intricately connected to hormonally regulated angiogenic response. Recent advances in the post genomic revolution have significantly impacted our understanding of ovarian function. In an angiogenesis perspective, the ovary offers a unique opportunity to unravel the molecular orchestration of blood vessel development and regression under normal conditions. A majority of ovarian cancers develop from the single layer of epithelium surrounding the ovaries. Angiogenesis is critical for the development of ovarian cancer and its peritoneal dissemination. The present review summarizes recent findings on the angiogenic response in neoplastic ovaries and discusses the prospects of using anti-angiogenic approaches to treat ovarian cancer.

Angiogenesis Inducing Agents↗
PubMed2001

Efficacy and safety of moricizine in the maintenance of sinus rhythm in patients with recurrent atrial fibrillation.

Maintenance of sinus rhythm is the primary goal of antiarrhythmic drug therapy for recurrent atrial fibrillation (AF). However, concern about proarrhythmic and negative inotropic effects has led to increasing reluctance to administer antiarrhythmic agents for this non-life-threatening arrhythmia. Moricizine is well tolerated in a wide variety of patients, and therefore, may be a safe and effective agent for treating AF. We retrospectively assessed the efficacy and safety of moricizine (mean dose 609 +/- 9 mg/day) in 85 consecutive patients with recurrent AF (2.6 +/- 0.5 years duration, 1.6 +/- 1 failed antiarrhythmic drugs). Structural heart disease was present in 69 (81%), but no recent myocardial infarct (< or =90 days) was present; mean left atrial size was 46 +/- 1 mm, and mean left ventricular ejection fraction was 0.51 +/- 0.01. Moricizine was discontinued because of unsuccessful direct-current cardioversion (n = 5) or clinically unacceptable side effects (n = 6); 6 patients developed transient side effects not requiring discontinuation. Of the 74 patients continuing therapy, 68% remained in sinus rhythm after 6 months, and 59% after 12 months. During a follow-up (21 +/- 2 months), there were neither deaths nor adverse effects requiring discontinuation of therapy. Thus, moricizine was effective, safe, and well tolerated in our patient cohort with AF.

Adult↗
PubMed2001

[Treatment with enoxaparin adapted to the fertility programs in women with recurrent abortion and thrombophilia].

Acquired and inherited thrombophilia are associated with recurrent pregnancy loss (RPL). Antithrombotic therapy could restore hemostatic balance and improve early placentation and gestational outcome. We evaluated the efficacy of enoxaparin adapted to the fertility program for prevention of pregnancy loss in 35 women (W) with early RPL and thrombophilia. Previous to the diagnosis of thrombophilia, they had had a total of 105 gestations of which 89 (85%) ended in early pregnancy loss. After diagnosis of thrombophilia, 35 subsequent pregnancies were treated with enoxaparin. In 5 cases assisted reproductive techniques were necessary to achieve pregnancy due to couple infertility. In 17 W who had had at least one preclinical pregnancy loss, enoxaparin (20 mg/d/s.c.) was started previous to conception and adapted to the fertility program. All the women continued with the gestational regime. Eighteen W with only clinical pregnancy loss started enoxaparin (20 mg twice per day s.c.) after biochemical pregnancy diagnosis. During gestations heparin dose was adjusted with anti Xa test, maintaining a range between 0.3 at 0.6 u/ml. With antithrombotic therapy, 30/35 (85%) of the pregnancies ended in live birth versus 16/105 (15%) of the pregnancies without treatment (p < 0.001). These results suggest that enoxaparin adapted to the fertility program can be effective in the prevention of preclinical and clinical abortion in women with thrombophilia.

Abortion, Habitual↗
PubMed2000

End-of-life care in the pediatric intensive care unit after the forgoing of life-sustaining treatment.

OBJECTIVE: To describe the attitudes and practice of clinicians in providing sedation and analgesia to dying patients as life-sustaining treatment is withdrawn. STUDY DESIGN: Prospective case series of 53 consecutive patients who died after the withdrawal of life-sustaining treatment in the pediatric intensive care unit at three teaching hospitals in Boston. Data on the reasons why medications were given were obtained from a self-administered anonymous questionnaire completed by the critical care physician and nurse for each case. Data on what medications were given were obtained from a review of the medical record. RESULTS: Sedatives and/or analgesics were administered to 47 (89%) patients who died after the withdrawal of life-sustaining treatment. Patients who were comatose were less likely to receive these medications. Physicians and nurses cited treatment of pain, anxiety, and air hunger as the most common reasons, and hastening death as the least common reason, for administration of these medications. Hastening death was viewed as an "acceptable, unintended side effect" of terminal care by 91% of physician-nurse matched pairs. The mean dose of sedatives and analgesics administered nearly doubled as life-support was withdrawn, and the degree of escalation in dose did not correlate with clinician's views on hastening death. CONCLUSION: Clinicians frequently escalate the dose of sedatives or analgesics to dying patients as life-sustaining treatment is withdrawn, citing patient-centered reasons as their principle justification. Hastening death is seen as an unintended consequence of appropriate care. A large majority of physicians and nurses agreed with patient management and were satisfied with the care provided. Care of the dying patient after the forgoing of life-sustaining treatment remains underanalyzed and needs more rigorous examination by the critical care community.

Analgesics↗
PubMed2000

Ligand design package (Ludi--MSI) applied to known inhibitors of the HIV-1 protease. Test of performance.

Performance of the Ludi (Insight II--MSI, ver. 98.0) program for computer-aided Ligand Design was tested using four crystallographic complexes of inhibitors with the HIV-1 protease. Possibility of reconstruction of the side chains and the peptide bond of the inhibitors, as well as attempt to construct de novo the central parts of these inhibitors, starting from the native structure of the enzyme, was studied. Results points that Ludi, although helpful, is merely initial tool for computer aided drug design. Moreover, some improvement of the program code is needed.

Drug Design↗
PubMed1999

Thermodynamic linkage between the binding of protons and inhibitors to HIV-1 protease.

The aspartyl dyad of free HIV-1 protease has apparent pK(a)s of approximately 3 and approximately 6, but recent NMR studies indicate that the aspartyl dyad is fixed in the doubly protonated form over a wide pH range when cyclic urea inhibitors are bound, and in the monoprotonated form when the inhibitor KNI-272 is bound. We present computations and measurements related to these changes in protonation and to the thermodynamic linkage between protonation and inhibition. The Poisson-Boltzmann model of electrostatics is used to compute the apparent pK(a)s of the aspartyl dyad in the free enzyme and in complexes with four different inhibitors. The calculations are done with two parameter sets. One assigns epsilon = 4 to the solute interior and uses a detailed model of ionization; the other uses epsilon = 20 for the solute interior and a simplified representation of ionization. For the free enzyme, both parameter sets agree well with previously measured apparent pK(a)s of approximately 3 and approximately 6. However, the calculations with an internal dielectric constant of 4 reproduce the large pKa shifts upon binding of inhibitors, but the calculations with an internal dielectric constant of 20 do not. This observation has implications for the accurate calculation of pK(a)s in complex protein environments. Because binding of a cyclic urea inhibitor shifts the pK(a)s of the aspartyl dyad, changing the pH is expected to change its apparent binding affinity. However, we find experimentally that the affinity is independent of pH from 5.5 to 7.0. Possible explanations for this discrepancy are discussed.

HIV Protease Inhibitors↗
PubMed1998

Expression of 15-lipoxygenase by human colorectal carcinoma Caco-2 cells during apoptosis and cell differentiation.

We studied arachidonic acid metabolism and the expression of cyclooxygenase (Cox) and 15-lipoxygenase (15-LO) in the human colorectal carcinoma cell line, Caco-2, which undergo apoptosis and cell differentiation in the presence of sodium butyrate (NaBT). Caco-2 cells expressed very low levels of Cox-1 but highly expressed Cox-2. NaBT treatment shifted the arachidonic acid metabolites by cell lysates from prostaglandins to 15-hydroxyeicosatetraenoic acid, indicating the presence of a 15-LO. Linoleic acid, an excellent substrate for 15-LO, was metabolized poorly by the Caco-2 cells, but NaBT treatment shifted metabolism to 15-LO metabolite, 13(S)-hydroxyoctadecadienoic acid. Caco-2 cells expressed a 15-LO but only after treatment with NaBT, as determined by Northern blotting. Immunoblotting with anti-human 15-LO antibody detected a 72-kDa band in NaBT-treated Caco-2 cells. Expression of 15-LO mRNA was dependent on the duration of NaBT treatment, with the highest expression observed between 10 and 24 h. Results from expression and metabolism studies with arachidonic and linoleic acid cells indicated Cox-2 was responsible for the lipid metabolism in control cells, whereas 15-LO was the major enzyme responsible after NaBT induction of apoptosis and cell differentiation. The 15-LO in Caco-2 cells was characterized as human reticulocyte 15-LO by reverse transcription-polymerase chain reaction and restriction enzyme analysis. The expression of 15-LO and 15-hydroxyeicosatetraenoic acid or 13(S)-hydroxyoctadecadienoic acid formation correlates with cell differentiation or apoptosis in Caco-2 cells induced by NaBT. The addition of nordihydroguaiaretic acid, a lipoxygenase inhibitor, significantly increased NaBT-induced apoptosis, whereas the addition of indomethacin did not alter NaBT-induced apoptosis in the Caco-2 cells. However, indomethacin treatment decreased the expression of Cox-2 in NaBT-treated cells and significantly increased the expression of 15-LO during NaBT treatment. These studies suggest a role for 15-LO, in addition to Cox-2, in modulating NaBT-induced apoptosis and cell differentiation in human colorectal carcinoma cells.

Apoptosis↗
PubMed1998

Acquisition of the Ph chromosome and BCR-ABL fusion product in AML-M2 and t(8;21) leukemia: cytogenetic and FISH evidence for a late event.

A patient with the M2 subtype of AML who had a 45,X,-X,t(8;21) karyotype at diagnosis was found to have the Ph chromosome in one out of 37 evaluated cells 18 months after the initial diagnosis. Interphase FISH studies utilizing a BCR-ABL dual-color probe did not detect a fusion product 4 months prior to the appearance of one Ph-positive cell. Nineteen months post diagnosis and 5 months after clinical relapse all evaluated cells had the Ph chromosome in a clone characterized by t(8;21). These observations suggest that late appearing Ph is a secondary event which may be either therapy-related or consistent with one of the later events in a multistep pathogenesis of AML.

Adult↗
PubMed1997

Analysis of the structure of chemically synthesized HIV-1 protease complexed with a hexapeptide inhibitor. Part I: Crystallographic refinement of 2 A data.

The structure of a complex between a hexapeptide-based inhibitor, MVT-101, and the chemically synthesized (Aba 67,95,167,195; Aba: L-alpha-amino-n-butyric acid) protease from the human immunodeficiency virus (HIV-1), reported previously at 2.3 A has now been refined to a crystallographic R factor of 15.4% at 2.0 A resolution. Root mean square deviations from ideality are 0.18 A for bond lengths and 2.4 degrees for the angles. The inhibitor can be fitted to the difference electron density map in two alternative orientations. Drastic differences are observed for positions and interactions at P3/S3 and P3'/S3' subsites of the two orientations due to different crystallographic environments.

Crystallography, X-Ray↗
PubMed1997

A physiologic in vitro model of the inferior vena cava with a computer-controlled flow system for testing of inferior vena cava filters.

RATIONALE AND OBJECTIVES: The authors develop a physiologic in vitro model of the inferior vena cava (IVC) for testing of filters. METHODS: The model is driven by a centrifugal pump. A computer-controlled electromagnetic valve is used for generation of different flow patterns. Limitation of the pressure increase in case of IVC occlusion is achieved by a bypass circuit. A glycerin solution is used for perfusion. Artificial clots are made from polyacrylamide gel. Data acquisition includes continuous monitoring of flow and difference pressure over the filter and video recording of the testing events. RESULTS: The model can generate constant and pulsatile flows. The pressure increase can be limited to 70 mm Hg in case of occlusion. Calculation of the flow velocities in the IVC is possible. A classification of thrombus capturing is presented. The testing of most of the results are reproducible. CONCLUSIONS: The in vitro model simulates the physiologic conditions in the IVC. It can be used for comparative testing of different filters and the evaluation of new filter designs.

Blood Flow Velocity↗