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Biomedical subjects

R S Weinberg

Publications and source records attributed to R S Weinberg.

At least 19 recordsLinked to original sources

The effectiveness of psychological interventions in competitive sport.

The use of psychological interventions in competitive sport to enhance performance has become increasingly popular. However, the effectiveness of these interventions has been questioned by some sports psychologists. In general, educationally-based psychological interventions have produced significant increases in performance. Specifically, it was found that 38 of the 45 studies examined (85%) had found positive performance effects, although causality could only be inferred in 20 of these studies. These interventions could be classified as relaxation-based, cognitive, cognitive-behavioural or behavioural in nature. Although general support was provided for the effectiveness of psychological interventions in competitive sports, a number of methodological shortcomings limit the application of the findings. For example, future intervention research in competitive sport should employ more detailed manipulation checks, include follow-up assessments beyond a mere post-test, include placebo-control groups to control for expectancy effects and include more diverse samples. In addition to the empirical intervention research, recent research employing qualitative methodologies has greatly added to our understanding of the types of interventions and what type of sport psychology consultants most positively affect performance enhancement, as well as the personal growth of athletes. Continued quantitative and qualitative research needs to be conducted so that a better understanding is gained of how to conduct psychological interventions with athletes that will enhance performance as well as personal growth.

Behavior Therapy

Stem cell factor amplifies newborn and sickle erythropoiesis in liquid cultures.

A two-phase liquid-culture system was used to substantially amplify and differentiate erythroblasts, starting with mononuclear cells from the blood of normal adults, newborn infants, and patients with sickle cell anemia. After the first 7 days (phase 1), in medium plus fetal bovine serum (FBS) alone, or in combination with stem cell factor (SCF) or conditioned medium (CM), the cell number was unchanged, and the cells all looked like lymphocytes. These cells were then diluted into medium with erythropoietin (Ep) alone, with Ep and either SCF or CM, or in methylcellulose with the same factors (phase 2). After 14 days in liquid phase 2 with SCF and Ep, the cell numbers increased an average of 30-fold in the sickle, 24-fold in the newborn, and 4-fold in the normal adult cultures; almost all the cells were erythroblasts and erythrocytes. SCF in phase 1 increased the number of late progenitors (CFU-E) assayed in methylcellulose, with the largest number in sickle, followed by newborn cultures and then adult cultures. We conclude that erythroid progenitor cells survive for at least 7 days without Ep (but with FBS). Progenitor cells are amplified, particularly with SCF. Later in culture, SCF with Ep increases the final number of differentiated erythroid cells. Both the early and the late effects of SCF are most effective in sickle, followed by newborn cultures and then adult cultures.

Adult

Effects of treatment with 5-azacytidine on the in vivo and in vitro hematopoiesis in patients with myelodysplastic syndromes.

The myelodysplastic syndrome (MDS) comprises a group of clonal hematopoietic disorders derived from an abnormality affecting a multipotent hematopoietic stem cell. Despite trials testing numerous agents in patients with MDS, no single drug has yet emerged as the accepted standard of treatment. Observation and supportive care with blood products and antibiotics, when necessary, continue to be the mainstays of therapy. We administered 5-azacytidine, a cell-cycle specific ring analog of the pyrimidine nucleoside cytosine, as a continuous intravenous infusion, 75 mg/m2 per day for 7 days every 4 weeks. Patients had refractory anemia with excess blasts (RAEB) or refractory anemia with excess blasts in transformation (RAEB-T). Responses were seen in 21 (49%) of 43 evaluable patients: five (12%) in complete remission (CR, complete normalization of bone marrow and peripheral blood counts); 11 (25%) in partial remission (PR, > or = 50% restoration of the deficit from normal of all three peripheral blood cell lines, elimination of transfusion requirements, and a decrease in percentage bone marrow blasts by > or = 50% from prestudy values); five (12%) improved (> or = 50% restoration in the deficit from normal of one or more peripheral blood cell lines and/or a > or = 50% decrease in transfusion requirements). A trilineage improvement (CR and PR) occurred in 37% of the patients. The median survival for all patients was 13.3 months and the median duration of remission for those with CR and PR was 14.7 months. Mild to moderate nausea and/or vomiting was the most common side effect (63%). Myelosuppression, either bone marrow hypoplasia or drug related cytopenias requiring a reduction in the dose of azacitidine, occurred in only 33% of the patients. Prior to treatment, bone marrow erythroid progenitor cells were assayed in vitro. Colonies derived from erythroid burst-forming units (BFU-e) were undetectable in one patient and reduced in two. The number of colonies derived from erythroid colony-forming units (CFU-e)) were also reduced in two of the three patients. In the two patients with detectable colony growth prior to treatment, colony number decreased by day 8 of the first cycle, followed by a subsequent increase. Continued treatment with azacitidine led to normalization of the number of CFU-e derived colonies as well as an increase in the number of BFU-e derived colonies. This improvement in erythroid colony number correlated with the spontaneous rise in hemoglobin levels and red cell transfusion independence.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged

Effect of stem cell factor on in vitro erythropoiesis in patients with bone marrow failure syndromes.

Stem cell factor (SCF) enhances normal hematopoiesis. We examined its effect in vitro on bone marrow and blood progenitors from patients with inherited bone marrow failure syndromes, including 17 patients each with Diamond-Blackfan anemia (DBA) and Fanconi's anemia (FA), 3 with dyskeratosis congenita (DC), and 1 each with amegakaryocytic thrombocytopenia (amega) and transient erythroblastopenia of childhood (TEC). Mononuclear cells were cultured with erythropoietin (Ep) alone or combined with SCF or other factors. SCF increased the growth of erythroid progenitors in cultures from 50% of normal controls, 90% of DBA, 70% of FA, 30% of DC, and the amega and TEC patients; normal numbers were reached in 25% of DBA studies. Improved in vitro erythropoiesis with SCF in all types of inherited marrow failure syndromes does not suggest a common defect involving kit or SCF, but implies that SCF may be helpful in the treatment of hematopoietic defects of varied etiologies.

Adolescent

Erythropoiesis is distinct at each stage of ontogeny.

In vitro erythropoiesis from fetuses, newborn infants, and adults was compared in methyl cellulose cultures. Fetal and newborn blood erythroid colony formation tended to be more sensitive to erythropoietin than adult. The day of maximal colony formation was earlier in fetal than in newborn or adult cultures. The number of colonies/100,000 mononuclear cells on d 13 of culture and on the day of peak growth was highest in fetal, intermediate in newborn, and lowest in adult cultures. Burst forming units-erythroid/mL of blood on culture d 13 and the day of peak growth were similar in fetuses and newborns, and both were significantly greater than in adults. The proportional synthesis of gamma-globin in fetal colonies was 2-fold greater than in newborn colonies, and 6-fold greater than in adult colonies. Thus, fetal, newborn, and adult erythroid progenitor cultures are each unique with regard to erythropoietin sensitivity, growth time course, number of erythroid colonies, and the proportion of gamma-globin synthesis.

Adult

Sickle and thalassemic erythroid progenitor cells are different from normal.

Blood erythroid progenitors (BFU-E) from patients with sickle and thalassemic syndromes were compared with those from normal individuals. The day of maximal colony formation in methyl cellulose was slightly later in the cultures from the patients with hemoglobinopathies than in the normal cultures. The number of colonies/100,000 mononuclear cells was similar in all cultures on day 13, but was higher in the hemoglobinopathy cultures on the day of maximal growth. The number of BFU-E/mL of blood was significantly higher than normal at all times in both sickle cell anemia and thalassemia. The proportional synthesis of gamma globin was twice normal in all sickle cultures, and 4 times normal in those from beta+-thalassemia. Hemin and interleukin-3 increased the numbers of erythroid colonies in all cultures, but did not consistently alter the globin synthesis patterns. Each progenitor population has a unique pattern in terms of time course, number of BFU-E, and level of gamma globin synthesis. These features indicate distinct types of BFU-E, or differences in accessory cells, or both, which distinguish blood-borne erythropoiesis in normals and those with hemoglobinopathies.

Adolescent

Erythropoiesis in Fanconi's anemia.

Fanconi's anemia (FA) is an autosomal recessive condition in which greater than 90% of the homozygotes develop aplastic anemia. To determine the relation between erythroid progenitors and clinical status, blood and marrow mononuclear cells were cultured in methyl cellulose with erythropoietin, plus other hematopoietic growth factors, and growth in normal oxygen (20%) was compared with growth in low, physiologic oxygen (5%). Peripheral blood cultures were performed from 24 patients, and marrows from six. Patients were classified into six clinical groups. Group 1: Severe aplasia, transfused; one patient; no erythroid progenitors. Group 2: Severe, transfused, androgen unresponsive; one patient; no blood burst-forming units-erythroid (BFU-E). Group 3: Androgen responsive; eight patients, with decreased blood BFU-E. Group 4: Aplastic, about to start treatment; two patients; below normal numbers of colony-forming units-erythroid (CFU-E) and BFU-E. Group 5: Stable, with mild anemia, and/or thrombocytopenia, and/or macrocytosis; seven patients; with below normal numbers of blood BFU-E. Group 6: Hematologically normal; five patients; blood BFU-E low normal to normal. One marrow had normal numbers of CFU-E and BFU-E. Incubation in 5% oxygen doubled CFU-E and BFU-E only in the patients with close to normal or normal growth in 20% oxygen. Hemin and interleukin-3 increased growth slightly in those cultures where there was some growth with erythropoietin alone. Our data show that there is a correlation between current clinical status and in vitro erythropoiesis. Cultures of erythroid progenitors may also be useful predictors of hematologic prognosis in FA, although our follow-up period is too short to prove this hypothesis.

Adolescent

Coryneform group A-4 endophthalmitis. An experimental animal model.

Diphtheroids, members of the coryneform family of bacteria, increasingly have been recognized as the cause of serious ocular diseases. After isolation of coryneform group A-4 from two patients with delayed endophthalmitis after cataract extraction and intraocular lens implantation, 10(7) organisms were injected into the vitreous of seven New Zealand white rabbits, producing endophthalmitis in all eyes inoculated. Coryneform group A-4 subsequently was isolated in six of seven eyes receiving 10(7) organisms, proving Koch's postulates. Five of these seven eyes were treated with a single dose of intravitreal gentamicin, and three eyes remained culture positive. Eyes inoculated with 10(5) or 10(2) coryneform group A-4 organisms had transient anterior chamber and vitreal inflammation; all vitreous cultures were negative. These studies demonstrate that coryneform group A-4 endophthalmitis can be reproduced in an animal model and that gentamicin may not sterilize an eye infected with this organism. Future studies are needed to determine the optimum antibiotic regimen for treatment of this type of endophthalmitis.

Animals

Coryneform endophthalmitis. Two case reports.

Recent clinical studies have emphasized the importance of diphtheroids, previously regarded as nonpathogenic bacteria or contaminants, as causes of ocular disease. We encountered two patients with endophthalmitis following cataract extraction and anterior chamber intraocular lens implantation. Both patients had previously been treated with subconjunctival and/or oral corticosteroids for presumed sterile endophthalmitis. Vitreous cultures in each case yielded pure growth of a diphtheroid that was subsequently identified as coryneform group A-4. The clinical response to standard intraocular therapy with gentamicin and cefazolin was delayed, although both patients eventually had restoration of functional vision. A comparison of the antibiotic minimum inhibitory and minimum bactericidal concentrations of the isolates may help to explain the delayed response to therapy seen in these two patients.

Aged

Effects of hemin on erythropoiesis.

It is clear that in vitro hemin increases the number of blood BFU-E derived colonies from normal donors. This occurs with sickle donors as well, despite the increased levels of hemin in vivo in these patients. The effect of hemin on relative gamma globin synthesis is inconsistent, however. In a few cases, delayed addition of hemin led to increased gamma globin synthesis. In time course studies of cultures from normal donors, hemin added on day 0 shifted the day of peak colony number from 13-14 to 16-20 days. The temporal decline in gamma globin synthesis was not altered. In cultures from sickle donors we found that the time for maximal colony number was later than in normals, occurring at 16-20 days even without hemin, and was not further delayed by hemin. The relative proportion of gamma globin synthesis was higher on day 14 in the sickle than the normal cultures, and the temporal decline was somewhat slowed in the sickle cultures by hemin. The elevated gamma synthesis and the later time for peak colony growth in the sickle cultures suggest that the erythroid progenitors in the blood of the sickle patients are less mature than those from normal individuals. There are several possible explanations for the detection of increased numbers of colonies in cultures containing hemin. Hemin may delay the final maturation of erythroblasts within erythroid colonies, thus shifting the time of maximal growth. It may also increase the extent of final maturation, leading to more complete hemoglobinization of the erythroblasts within the colonies, and thus increasing the number of colonies that are eventually recognized as erythroid.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured

Comparison of erythroid progenitor cell growth in vitro in polycythemia vera and chronic myelogenous leukemia: only polycythemia vera has endogenous colonies.

The ability of erythroid cultures to distinguish among myeloproliferative disorders was examined. We studied 14 patients with polycythemia vera (PV), 11 with chronic myelogenous leukemia (CML), four with non-PV erythrocytosis, two with agnogenic myeloid metaplasia, as well as three normal fetuses and greater than 25 normal adults. Endogenous, i.e. grew without added erythropoietin, bone marrow CFU-E-derived colonies were observed in all but one PV patient. However, endogenous blood BFU-E-derived bursts were observed in only eight of 14 PV patients. Endogenous erythroid colonies were not seen in cultures from any normal adults or fetuses, or patients with CML, erythrocytosis, or myeloid metaplasia. In PV, relative HbF synthesis was always greater in cultures without erythropoietin, while in cultures from all other patients relative HbF synthesis was similar to that observed in cultures from normal individuals. We conclude that PV and CML are distinguishable in culture since CML patients do not have endogenous growth. Most important, endogenous bone marrow CFU-E-derived colonies are the only consistently unique observation in patients with PV, and endogenous CFU-E- and BFU-E-derived colonies and bursts are not uniformly observed in PV blood cultures. In-vitro studies of erythropoiesis to confirm the diagnosis of PV, therefore, require marrow when endogenous colonies and bursts are absent from blood cultures.

Adolescent

Toxoplasmic scleritis.

Although toxoplasmosis is the most common infectious cause of posterior intraocular inflammation, it is rarely described in association with scleritis. The authors present five cases of toxoplasmosis with scleritis. Two of the five cases were diagnosed clinically and serologically as having toxoplasmosis. Their retinochoroiditis and scleritis responded well to medical therapy. Retinochroiditis and scleritis that was refractory to treatment developed in the other three patients, two of whom had been receiving immunosuppressive therapy for systemic diseases. Their therapeutic regimens did not include treatment for toxoplasmosis. All three eyes became blind and were enucleated. Results of pathologic examination of all three enucleated eyes showed Toxoplasma gondii in the retina. There was severe inflammation of the retina, choroid, and sclera. Toxoplasmosis should be considered in the clinical differential diagnosis of scleritis associated with retinochoroiditis, particularly in immunosuppressed patients.

Adult

Nocardial endophthalmitis: report of two cases studied histopathologically.

We report two cases of nocardial endophthalmitis. Case 1 is a 66-year-old man whose left eye was enucleated about one month after onset of decreased vision. Ophthalmoscopic examination disclosed multiple choroidal masses. Six weeks before the onset of ocular manifestations he had undergone a prolonged carotid endarterectomy with intraoperative complications. The source of the ocular infection was probably exogenous. Case 2 is a 49-year-old woman who had systemic sclerosis (scleroderma) with severe pulmonary insufficiency. She had received moderate doses of corticosteroids. Seventeen months after initiation of therapy she developed ocular manifestations leading to enucleation of the eye one month later. Histopathologically, the enucleated eyes in both cases showed numerous branching, Gram-positive, filamentous organisms involving mainly the plane of Bruch's membrane and the subretinal space. The nosological and microbiological aspects of nocardiosis are reviewed.

Aged

The effect of hemin in vitro and in vivo on human erythroid progenitor cells.

Hemin stimulates erythropoiesis and hemoglobin synthesis in vitro. We cultured erythroid progenitor cells from normal individuals, patients with sickle cell anemia, and a patient with acute variegate porphyria who received intravenous hemin treatment, with 0-800 microM hemin added in vitro. Fifty to 200 microM hemin consistently stimulated colony growth from normal donors 2- to 8-fold, while concentrations of up to 400 microM were stimulatory in cultures from donors with sickle cell anemia. In vivo hemin decreased the number of blood BFU-e in the patient with porphyria, but did not abrogate the in vitro stimulatory effect of hemin. Hemin concentrations which increased colony numbers increased gamma globin synthesis in some studies and decreased it in others. Hemin thus has clearcut erythroid growth-potentiating activity, although a consistent effect on globin chain regulation is not apparent.

Adult