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Biomedical subjects

M Goldman

Publications and source records attributed to M Goldman.

At least 199 records · Page 11Linked to original sources

Jugular venous blood flow velocity waveforms in human fetuses between 20 and 42 weeks of pregnancy.

BACKGROUND: The goal of the study was to measure the blood flow parameters of the fetal internal jugular vein during the second half of normal pregnancy using Doppler ultrasound. METHODS: Jugular blood flow was analyzed in 95 normal singleton fetuses between 20 and 42 weeks gestation. Color and pulsed Doppler ultrasound was used to obtain jugular venous waveforms at the level of the mid-neck. Peak velocities, ratios of velocities, and time-averaged maximum velocities were measured. RESULTS: Jugular venous waveforms in healthy fetuses consist of three phases--the first forward peak occurs during ventricle systole; the second forward peak occurs during early diastole and the third peak occurs during atrial contraction. Forty-eight percent of the fetuses demonstrated absent flow during atrial contraction; 32% of fetuses demonstrated forward flow during atrial contraction and finally 20% of fetuses demonstrated flow reversal during atrial contraction. CONCLUSIONS: The reported jugular venous profile may serve as a foundation for future studies of jugular blood flow in high risk fetuses.

Adult↗

The role of azole antifungal agents for systemic antifungal therapy.

Although amphotericin B remains the cornerstone of antifungal drug therapy, fluconazole and itraconazole have been found useful for long-term maintenance or prophylactic regimens. This article reviews characteristics of fluconazole and itraconazole and compares them with ketoconazole and amphotericin B.

Amphotericin B↗

Health impacts of large releases of radionuclides. Retrospective radiation dose assessment: an overview of physical and biological measures of dose.

Models to estimate population doses from environmental measurements, dietary radioactivity and lifestyle characteristics are useful for populations but difficult to apply accurately to an individual within the population. Individual biological and radiation dosimetry is limited to small numbers of persons and thus has limitations when considering larger groups or populations. Current direct biological indicators of dose are generally limited to doses above 0.1 Gy. New advances in improving the accuracy and sensitivity of these methods offer the promise of validating population estimates and specifying variance in individual doses. An integration of the two approaches will provide the support for more accurate radiation epidemiology and risk assessment.

Biomarkers↗

Anatomic variations of the musculocutaneous nerve in the arm.

To determine the course and anatomic relationships of the musculocutaneous nerve in the arm, we dissected 54 cadaver arms and measured the length of any interconnection between the musculocutaneous nerve and the median nerve (36% of dissections; mean, 1.77 cm) and the distance from the coracoid process to (1) the musculocutaneous nerve (mean, 0.46 cm distal); (2) the median nerve (mean, 1.91 cm distal); (3) the musculocutaneous nerve's entrance to and exit from the coracobrachialis muscle (mean, 4.99 cm and 7.55 cm, respectively); and (4) the musculocutaneous nerve's entrance into the biceps muscle (mean, 11.66 cm). The high percentage of anomalies found emphasizes the complexities and irregularities of this anatomic region with regard to surgical approaches.

Arm↗

Tolerance in liver transplantation: facts and perspectives.

Today, liver transplantation is the treatment of choice for most of the patients with endstage liver failure. Nevertheless, immunosuppressive regimens are not yet optimal; rejection still represents the first cause of graft loss, and infections and malignancies related to the non specific immunosuppression are a major source of morbidity and mortality. Therefore, the development of protocols aiming to induce transplantation tolerance--the survival of the graft without immunosuppression--represents a crucial challenge for the future. In the present report, we discuss two different approaches in this perspective. First, as compared with other organ, liver graft may present a particular propension to induce chimerism. As this phenomenon could promote allograft survival, the enhancement of chimerism by administration of donor cells, simultaneously with the transplantation, may constitute a new therapeutic strategy to induce tolerance. Second, experimental observations indicate that the initiation of the immune reaction in the liver may preferentially induce a TH2-type response. As TH2 lymphocytes are poor effector of acute rejection, this phenomenon could contribute to the spontaneous survival of liver graft and their tolerogenic effect observed under some experimental conditions. However, the capacity of TH2 cells to induce lymphoproliferative disease and their possible role in chronic rejection will probably represent a major limitation for clinical use of this strategy.

Animals↗

Biological predictors of 1-year outcome in schizophrenia in males and females.

This paper describes a prospective study designed to ascertain the predictive value of biological factors associated with schizophrenia in males and females. In a sample of 59 medication-free schizophrenic inpatients (41 males; 18 females), we assessed the correlation of four factors--rapid eye movement (REM) sleep latency, delta (slow-wave) sleep, dexamethasone suppression test (DST) cortisol levels, and ventricle-brain ratio (VBR)--with several dimensions of outcome at 1-year post-discharge. In the total sample, shorter REM latency was associated with poor outcome on all dimensions measured: rehospitalization, employment, social activity, symptomatology, and global functioning. However, none of the other biological factors were associated with any measure of outcome. The predictive value of REM latency appeared to be gender-specific; in general, the relationships between reduced REM latency and poor outcome were consistently noted in females, but were not significant in males. These results suggest that a common, possibly gender-related, pathophysiological mechanism might underlie both abnormal REM latency and poor outcome. The findings underscore the importance of considering gender differences in studies of schizophrenia.

Electroencephalography↗

VBR in schizophrenia: relationship to family history of psychosis and season of birth.

Ventricular enlargement has been consistently demonstrated in schizophrenia using both CT and MRI. Despite this, the structural changes that underlie increased ventricle-brain ratio (VBR) and its relationship to environmental factors (intrauterine viral exposure, obstetric complications, etc.) and family history of schizophrenia remain poorly defined. Increased VBR has been shown in some studies to correlate with an absence of family history of schizophrenia and with Winter-Spring birth. In an attempt to obtain a clearer picture of the contribution of environmental and genetic factors to VBR, we studied 54 patients with DSM III-R schizophrenia. VBR was determined from head CT scans via computerized planimetry. Family history of psychosis and non-psychotic mood disorder was determined with the family informant method. Season of birth was encoded in several ways, including season, trimester and dichotomously. Patients without a family history of psychosis had significantly larger VBR than patients with such a history; family history of mood disorder was not related to VBR. Season of birth was not predictive of VBR. Family history of psychosis and season of birth were not related to each other. These results are in line with prior work demonstrating an association between increased VBR and sporadic (non-familial) schizophrenia. We did not find a relationship between VBR and season of birth, which suggests that risk of perinatal viral exposure and other seasonal environmental factors may not account for the ventricular enlargement in non-familial schizophrenia observed in our sample.

Adult↗

Adenosine enhances IL-10 secretion by human monocytes.

Adenosine is a potent endogenous antiinflammatory agent released by cells under metabolically unfavorable conditions. Its effects on the production of IL-10 by human monocytes were presently investigated. Pre-incubation with adenosine dose-dependently enhanced IL-10 release by TNF stimulated human monocytes (+29, +58, and +116% at 1, 10, and 100 muM, respectively.) Adenosine also significantly enhanced IL-10 production after hydrogen peroxide and LPS stimulation and dose-dependently inhibited TNF secretion. Pre-incubation was not mandatory to achieve these effects, since addition of adenosine at the time of or 30 min after the stimulus led to the same results. Blocking IL-10 with anti-IL-10 mAbs partially restored adenosine-induced TNF inhibition. The enhanced IL-10 production was not observed when cells were preincubated with adenosine A1 or A2 receptor agonists (R-phenylisopropyladenosine, 5'-N-ethylcarboxamido-adenosine, and 2-chloroadenosine) and was not affected by pretreatment with theophyllin, an antagonist of both A1 and A2 receptors, or with dipyridamole, an inhibitor of adenosine cellular uptake. In conclusion, adenosine, in the submillimolar concentration range, increases IL-10 secretion by stimulated monocytes. This phenomenon participates in TNF inhibition, a known property of adenosine, but is not mediated through the occupancy of A1 or A2 receptors. This may represent a novel antiinflammatory property of adenosine by which it could modulate inflammation and limit ischemia-reperfusion injury.

Adenosine↗

Monocyte procoagulant activity induced by in vivo administration of the OKT3 monoclonal antibody.

The first injection of OKT3 in kidney transplant recipients activates the common pathway of coagulation. This may result in early thrombosis of graft vessels. To this day, the cells involved in this phenomenon have not been identified. The aim of this study was to investigate whether circulating monocytes participated in this OKT3-induced coagulopathy. The procoagulant activity (PCA) of circulating monocytes rose from (mean +/- SEM) 0.15 +/- 0.02 mU/mL to 0.40 +/- 0.05 mU/mL at 3 hours (P = .002) and 0.56 +/- 0.21 at 5 hours (P = .045) after the initial OKT3 injection. These monocytes displayed increased tissue factor expression at the same moments (mean flourescence intensity: 14 +/- 2 before OKT3 injection versus 54 +/- 14 at 3 hours, P = .008 and 34 +/- 7 at 5 hours, P = .01). Tissue factor mRNA was detected in blood by reverse transcriptase-polymerase chain reaction as early as 2 hours after OKT3 administration. The circulating monocytes also displayed a steady increase in membrane expression upregulation of ICAM-1, CD29, CD11b, and CD11c. In vitro experiments showed that OKT3 as well as 2 mitogenic, humanized anti-CD3 antibodies potently induced monocytic PCA whereas the 4 nonmitogenic anti-CD3 antibodies tested were over 1,000-fold less potent than OKT3. We conclude that (1) OKT3 induces in vivo tissue factor gene upregulation and membrane expression resulting in increased PCA of circulating monocytes; and (2) nonmitogenic anti-CD3 antibodies seem devoid of significant procoagulant properties.

Blood Coagulation↗

Eosinophils express a functional receptor for interferon alpha: inhibitory role of interferon alpha on the release of mediators.

Recent reports describe the beneficial use of alpha interferon (IFNalpha) for the treatment of idiopathic hypereosinophilic syndrome (HES) unresponsive to conventional therapy. A clinical improvement associated with a rapid decrease of peripheral blood eosinophilia suggested possible direct effects of IFNalpha on eosinophils through the presence of IFNalpha receptors (IFNalphaR). Reverse transcriptase-polymerase chain reaction (RT-PCR) and cytochemistry were used respectively to detect the presence and define the distribution of IFNalphaR on enriched eosinophil preparations purified from blood cells. IFNalphaR was found on eosinophils collected from patients with various eosinophilic disorders. In addition, IFNalpha inhibited the release of eosinophil granule proteins such as eosinophil cationic protein (ECP), neurotoxin (EDN, or interleukin-5 (IL-5). Moreover, antiparasite cytotoxicity was also strongly reduced in a dose-dependent manner by IFNalpha. These results provide the first evidence that human eosinophils express a functional receptor for IFNalpha and represent a potential basis for the beneficial effects of IFNalpha in patients with hypereosinophilic syndromes.

Animals↗

The IgE humoral response in OKT3-treated patients. Incidence and fine specificity.

We recently described a case of anaphylaxis occurring at the time of retreatment with OKT3 of a renal allograft recipient in whom, for the first time, high anti-OKT3 IgE levels were documented. This led us to examine a large series of sera from 181 OKT3-treated patients to better define the frequency of IgE sensitization, its fine specificity (anti-isotypic and/or anti-idiotypic) and its relation to the appearance of IgG anti-OKT3 antibodies (Abs). Six patients out of the 181 assayed have developed anti-OKT3 IgE Abs as detected by ELISA. The earliest time of appearance of IgE anti-OKT3 Abs was 10 days after starting OKT3 (range, 10-25). The IgE response peaked by day 18 (range, 11-35) and had usually disappeared at 3 months after treatment. A more careful dissection of the fine specificity of the IgE response revealed that three of the four patients tested had developed an exclusive anti-idiotypic response. In the last patient, an anti-isotypic component was present since anti-OKT3 IgE Abs also reacted with control IgG2a, IgG2b, and IgG3 monoclonal antibodies. Importantly, anti-OKT3 IgE Abs were only detected in heavily sensitized patients also showing high titers of IgG specific Abs by ELISA (> or = 1/1000) as well as "blocking" anti-OKT3 antibodies, as assessed by immunofluorescence. We conclude that (1) exposure to OKT3 may lead to specific IgE sensitization that, however, only appears in about 38% of the patients; (2) IgE Abs mostly appear in patients also showing high levels of conventional IgG anti-OKT3 Abs including the presence of "blocking" anti-idiotypic Abs, and (3) IgE Abs may be directed to both idiotypic and isotypic determinants of the monoclonal antibody.

Animals↗