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Biomedical subjects

D Stein

Publications and source records attributed to D Stein.

At least 19 recordsLinked to original sources
PubMed1996

Long-term intermittent urokinase therapy in patients with end-stage coronary artery disease and refractory angina pectoris: a randomized dose-response trial.

OBJECTIVES: This dose-response study was designed to test two low dose regimens of urokinase administered over a prolonged time period in patients with chronic refractory angina pectoris with respect to effects on clinical symptoms and objective variables of myocardial ischemia. BACKGROUND: Patients with severe and chronic refractory angina pectoris in end-stage coronary artery disease represent an increasing clinical problem. Favorable therapeutic effects on myocardial ischemia have been reported for long-term application of low dose urokinase. METHODS: Ninety-eight patients with chronic refractory and end-stage coronary artery disease were randomly assigned to two treatment groups: group A (49 patients) received 50,000 IU and group B (49 patients) 500,000 IU of urokinase as an intravenous bolus infection three times a week over a period of 12 weeks. Variables evaluated were number of weekly anginal events, data from ergometric exercise testing with simultaneous electrocardiographic registration, semiquantitative evaluation of Tc-99m 2-methoxy isobutyl isonitrile (MIBI) scans and rheologic variables. RESULTS: After 12 weeks of treatment, anginal symptoms (events/week) were reduced significantly in group B by 70% compared with 24% in group A (p < 0.001). Fibrinogen decreased by 3% in group A and by 33% in group B (p < 0.001). Plasma viscosity and red blood cell aggregation were reduced by 6.4% (p < 0.001) and 19.9% (p < 0.001), respectively, in group B. Objective variables of myocardial ischemia were improved significantly in group B only. No cumulation of coronary ischemic events was observed in group B. CONCLUSIONS: Long-term intermittent urokinase therapy in an applied dose of 3 X 500,000 IU/week represents an effective anti-ischemic and antianginal approach for patients with refractory angina pectoris and end-stage coronary artery disease. Apart from rheologic improvement, antithrombotic properties and plaque regression are likely anti-ischemic mechanisms.

Aged↗
PubMed1995

Toxicity, biodistribution and radioprotective capacity of L-homocysteine thiolactone in CNS tissues and tumors in rodents: comparison with prior results with phosphorothioates.

L-Homocysteine thiolactone (L-HCTL) was evaluated for its potential as an intravenously-administered central nervous system (CNS) radioprotector in C3H mice and F344 rats. Toxicity assessments in the mouse yielded a LD50 of 297 mg/kg and in the rat 389 mg/kg. Biodistribution studies in tumor-bearing mice showed that brain specimens contained more label at 10 min than the tumors but less at 30 or 60 min. Brain uptake relative to the tumors, the brain/tumor ratio, ranged between 0.5 and 3.3. The cervical spinal cord of non-tumor-bearing rats was irradiated with 32 Gy 137Cs with or without prior treatment with L-HCTL following which the time to forelimb or hindlimb paralysis was measured to determine the relative protective factors (RPFs) for this radiation dose. For forelimb paralysis the RPF was 1.9 (+/- 1.0, SD) and for hindlimb it was 2.0 (+/- 1.1, SD). 36B-10 glioma cells irradiated in vitro with or without L-HCTL and assayed for colony forming capacity demonstrated a dose modifying factor (DMF) of only 1.15 (+/- 0.16, SE). Rats bearing intracerebral 36B-10 glioma received 137Cs irradiation with or without L-HCTL after which the tumors were similarly assayed in vitro. From this the glioma DMF was 1.2 (+/- 0.30, SE). Compared to prior results with phosphorothioates our data show that the toxicity of L-HCTL is roughly the same as WR2721, WR77913 and WR3689 and that it distributes at higher levels in the CNS after systemic administration. L-HCTL may well equal these phosphorothioates at protecting normal CNS tissue without requiring administration directly into the cerebrospinal fluid-containing spaces and it does not protect the 36B-10 glioma.

Amifostine↗
PubMed1995

In vivo effects of pentaerythrityl-tetranitrate and isosorbide-5-mononitrate on the development of atherosclerosis and endothelial dysfunction in cholesterol-fed rabbits.

We wished to determine whether long-term treatment with organic nitrovasodilators has pharmacological effects on the development of atherosclerotic lesions and endothelial dysfunction in cholesterol-fed rabbits. For 15 weeks, six groups of 9 New Zealand White rabbits received a standard diet, which contained no admixture, pentaerythrityl-tetranitrate (PETN 6 mg/kg body weight/day), or isosorbide-5-mononitrate (ISMN 2 mg/kg body weight/day). In the other three groups, the same diets were further enriched with cholesterol (0,75%). Four rings of thoracic aorta were used for tension studies; these rings and the aortas from the aortic arch to bifurcation were then fixed in formol and stained with Sudan IV to determine the area of luminal atherosclerotic lesions by a computerized laser-scanning approach. The cholesterol diet increased plasma levels of cholesterol from 69.8 +/- 10.4 to 907.1 +/- 85.5 mg/dl. A similar result was obtained in the group receiving PETN/cholesterol, but the group fed ISMN/cholesterol showed a significantly higher plasma level of cholesterol (1,165 +/- 81.4 mg/dl). Plasma levels of PETN metabolites were still detectable by gas chromatography/mass spectrometry after a 24-h in vivo washout period. The cholesterol diet induced a pronounced degree of atherosclerotic lesions in the aortic arch and the thoracic and abdominal aorta: 73.3 +/- 1.9, 46.3 +/- 2.5, and 49.6 +/- 3.6%, respectively. Additional treatment with PETN resulted in a reduction of this atherosclerotic area to 58.6 +/- 2.05% (p < 0.0001), 34.7 +/- 1.98% (p < 0.01), and 39.3 +/- 3.06% (p < 0.05). In contrast, ISMN had no significant effect on this parameter. The cholesterol diet also induced an endothelial dysfunction as indicated by the diminished vasorelaxation induced by acetylcholine (ACh). Treatment with PETN completely inhibited the development of endothelial dysfunction, whereas ISMN had no effect. In the three groups receiving a cholesterol diet, an increased extent of aortic lesions significantly correlated with increased endothelial dysfunction measured in the same preparations. The long-term treatment with PETN did not affect the vasorelaxing potency of PETN in aortic rings, and similar results were obtained in the case of ISMN. We conclude that long-term treatment with doses of PETN, which do not promote the development of in vitro vascular nitrate tolerance, may protect against atherosclerosis and endothelial dysfunction. This novel, yet unknown pharmacodynamic quality of nitrovasodilators like PETN may contribute to their long-term efficacy in coronary artery disease but may also imply new therapeutic indications in the future.

Acetylcholine↗
PubMed1995

Rupture of the right atrium secondary to blunt cardiac injury.

Occult cardiac injury following blunt trauma is underestimated in frequency of occurrence. Recent reports indicate that it rivals thoracic aortic transection as the cause of death following traffic fatalities. The most common mechanisms include rapid cardiac rotation while the great vessels remain fixed, transfer of hydraulic pressure from the abdomen or extremities, and direct myocardial compression by the sternum. Presentation can be diverse and findings can include jugular venous distention, upper extremity cyanosis, unexplained hypotension, and muffled heart sounds. An enlarged cardiac silhouette is occasionally seen on roentgenographic evaluation. A surprisingly large number of these patients are noted to have no significant signs of external thoracic trauma. Possible mechanisms include rapid rotation and deceleration of the heart with fixation of the great vessels, transmission of a large venous pressure wave to the heart following abdominal or extremity compression, and direct compression of the heart by the sternum. Following prompt diagnosis and rapid surgical intervention, a large number of these patients can be expected to survive this otherwise fatal injury.

Adult↗
PubMed1994

Monocyte adhesion in patients with bone marrow fibrosis is required for the production of fibrogenic cytokines. Potential role for interleukin-1 and TGF-beta.

Idiopathic myelofibrosis (IMF) is a hemologic disorder characterized by bone marrow (BM) fibrosis. The BM contains excessive deposits of extracellular matrix proteins and exhibits neovascularization. The fibrosis is hypothesized to be a reactive phenomenon secondary to a clonal myeloid disorder. Growth factors such as platelet-derived growth factor (PDGF), TGF-beta, and epidermal growth factor have been postulated as potential agents involved in BM fibrosis. We studied the induction of two fibrogenic cytokines, IL-1 and TGF-beta, in IMF monocytes. High levels of both cytokines were produced in unstimulated IMF monocytes, compared with background levels produced in normal controls. Most of the TGF-beta produced by IMF monocytes was in its active form. The spontaneous induction of IL-1 alpha, IL-1 beta, and TGF-beta in IMF monocytes parallels an increase in their steady state mRNA. Although high levels of cytoplasmic IL-1 alpha, IL-1 beta, and TGF-beta protein were detected in monocytes that were not subjected to any form of adherence, the secretion of these cytokines required adhesion. High levels of fibronectin, hyaluronic acid, and collagen, all potential ligands for the CD44 adhesion molecule, have been reported in the circulation of IMF patients. However, the Ab-binding capacity of CD44 in IMF monocytes was reduced by 50% when compared with normal controls. Our results indicate that monocytes and adhesion molecules may play a role in the induction of fibrogenic cytokines. These parameters may be important to the pathophysiology of BM fibrosis.

Adult↗
PubMed1994

The SH2 domain protein GRB-7 is co-amplified, overexpressed and in a tight complex with HER2 in breast cancer.

SH2 domain proteins are important components of the signal transduction pathways activated by growth factor receptor tyrosine kinases. We have been cloning SH2 domain proteins by bacterial expression cloning using the tyrosine phosphorylated C-terminus of the epidermal growth factor receptor as a probe. One of these newly cloned SH2 domain proteins, GRB-7, was mapped on mouse chromosome 11 to a region which also contains the tyrosine kinase receptor, HER2/erbB-2. The analogous chromosomal locus in man is often amplified in human breast cancer leading to overexpression of HER2. We find that GRB-7 is amplified in concert with HER2 in several breast cancer cell lines and that GRB-7 is overexpressed in both cell lines and breast tumors. GRB-7, through its SH2 domain, binds tightly to HER2 such that a large fraction of the tyrosine phosphorylated HER2 in SKBR-3 cells is bound to GRB-7. GRB-7 can also bind tyrosine phosphorylated SHC, albeit at a lower affinity than GRB2 binds SHC. We also find that GRB-7 has a strong similarity over > 300 amino acids to a newly identified gene in Caenorhabditis elegans. This region of similarity, which lies outside the SH2 domain, also contains a pleckstrin homology domain. The presence of evolutionarily conserved domains indicates that GRB-7 is likely to perform a basic signaling function. The fact that GRB-7 and HER2 are both overexpressed and bound tightly together suggests that this basic signaling pathway is greatly amplified in certain breast cancers.

3T3 Cells↗
PubMed1994

[Self-castration].

Self-castration has been described in different eras and societies. It usually occurs in transsexualism, serious personality disorders and psychosis. It is not impulsive, but the result of long-standing conflicts, usually involving difficulties with male identity and inability to cope with sexual drives. Schizophrenics usually act under the influence of delusions and hallucinations. The medical and social attitudes to self-castration are never unequivocal. There are 60 case reports in the psychiatric literature. We describe a 35-year-old schizophrenic who castrated himself.

Hallucinations↗
PubMed1994

The attitude of asthmatic and nonasthmatic adolescents toward gymnastic lessons at school.

Questionnaires examining attitudes to physical activity and to gymnastic lessons at school were filled out by 37 asthmatic and 36 healthy adolescents. No significant differences were demonstrated between the two groups. The study suggests that if a positive approach to physical activity is associated with active involvement, attitudinal factors per se should not mitigate against active participation of asthmatic subjects in sports.

Adolescent↗
PubMed1994

Quality improvement in the biomedical communications audio visual unit.

The audio visual unit is a highly visible and most frequently requested service provided by a biomedical communications department. To continuously improve service, delivery, and operation of an audio visual communications function is a challenge. This article presents a field-tested audit tool for describing audio visual unit strengths and limitations. The tool suggests four assessment areas: the service plan, the client communication network, training and managing staff, and standard operating policy and procedures.

Audiovisual Aids↗
PubMed1994

Akathisia and pseudoakathisia: clinical observations and accelerometric recordings.

BACKGROUND: Akathisia is a common side effect of neuroleptic treatment that is diagnosed on the basis of clinical observations. Its definition is regarded as complex and controversial. Thus, for example, while some authorities see akathisia as strictly an abnormal subjective state, others require the inclusion of specific repetitive movements. The present study suggests that the addition of objective accelerometric recordings to standardized clinical observations may increase the validity of this diagnosis. METHOD: Sixteen chronic schizophrenic patients, treated with various neuroleptic medications, were diagnosed as suffering from akathisia. The diagnosis was based on detailed clinical observations performed according to accepted diagnostic criteria. All patients underwent repeated accelerometric recordings following the onset of akathisia. RESULTS: While most subjects suffered from lower limb akathisia, 5 patients demonstrated the involvement of other body segments. Akathisia most frequently appeared while the patients were seated. The abnormal movements were regular, nonparoxysmal, and intermittent. Most patients suffered from a tardive disorder. The accelerometric recordings demonstrated in all cases a constant and regular wave form, frequency (below 4 Hz), and amplitude. The findings were reproducible, i.e., similar patterns appeared in several recordings of the same patient during the abnormal movements. CONCLUSION: Extensive and detailed clinical evaluations reveal that akathisia is not necessarily associated with restless pacing. Rather, the syndrome may include periodic, regular, and stereotyped movements, appearing in different body segments. Accelerometric recordings seem to confirm the clinical diagnosis of akathisia, demonstrating the existence of a constant wave form, frequency, and amplitude. In addition, these techniques may distinguish between akathisia and other disorders e.g., neuroleptic-induced tremor or tardive dyskinesia.

Adult↗
PubMed1994

Antithrombin III and trauma patients: factors that determine low levels.

A prospective (cohort) study was conducted to determine the incidence of low antithrombin III (AT III) levels and the association with selected clinical variables in adult trauma patients. One hundred sixty AT III levels were obtained on 50 consecutive trauma admissions to a community-based level I trauma center. Antithrombin III levels were drawn as soon after admission as possible and every other day thereafter. Thirty-one patients (62%) had at least one low AT III level (< 80%), whereas 15 concurrently drawn control levels were all > or = 90%. Low AT III levels were more common in patients with one or more of the following: base deficit less than -4 (39% vs. 0, p = 0.002); Injury Severity Score > 15 (48% vs. 16%, p = 0.04); and blood transfusion (32% vs. 5%, p = 0.04). All other variables (shock, surgical intervention, subcutaneous heparin, and sequential compression devices) were not statistically significant, although all six patients with shock had low levels. In conclusion, over 60% of adult trauma patients had low AT III levels at some time during hospitalization and these patients were clearly more severely injured. Further studies are required to determine if these patients are more susceptible to thromboembolic phenomena.

Adult↗
PubMed1993

Engineering resistance to 'aging' of phosphylated human acetylcholinesterase. Role of hydrogen bond network in the active center.

Recombinant human acetylcholinesterase (HuAChE) and selected mutants (E202Q, Y337A, E450A) were studied with respect to catalytic activity towards charged and noncharged substrates, phosphylation with organophosphorus (OP) inhibitors and subsequent aging of the OP-conjugates. Amino acid E450, unlike residues E202 and Y337, is not within interaction distance from the active center. Yet, the bimolecular rates of catalysis and phosphylation are 30-100 fold lower for both E450A and E202Q compared to Y337A or the wild type and in both mutants the resulting OP-conjugates show striking resistance to aging. It is proposed that a hydrogen bond network, that maintains the functional architecture of the active center, involving water molecules and residues E202 and E450, is responsible for the observed behaviour.

Acetylcholinesterase↗