Biomedical subjects

S Stein

Publications and source records attributed to S Stein.

At least 37 records · Page 2Linked to original sources

PubMed2001

Phase II trial of toremifene in androgen-independent prostate cancer: a Penn cancer clinical trials group trial.

Toremifene has antiestrogenic and estrogenic properties in vitro and in vivo. In addition, it may have antiangiogenesis and antimicrotubule properties at higher doses. Studies have demonstrated the efficacy of this agent in the treatment of metastatic breast cancer. We performed a phase II trial of toremifene in patients with androgen-independent prostate cancer (AIPC). Patients with an increasing prostate-specific antigen level despite castrate testosterone levels and antiandrogen withdrawal were eligible. Patients could not have received prior salvage hormonal therapy or chemotherapy. Patients received toremifene at 300 mg/m2/d orally (maximum dose 640 mg/d). Fifteen patients were treated. Patients received treatment for a median of 13 weeks (range, 4-30 weeks). The median age was 72 years (range, 58-80 years). The median Eastern Cooperative Oncology Group performance status was 0. The treatment was well tolerated and toxicity was mild. Two patients had grade III hepatic toxicity; one had grade III hyperglycemia. There were no treatment-related deaths. No objective responses were demonstrated. In summary, toremifene is not effective therapy for AIPC at the dose and schedule evaluated in this trial.

Aged↗

PubMed2000

An IL6 promoter polymorphism is associated with a lifetime risk of development of Kaposi sarcoma in men infected with human immunodeficiency virus.

Kaposi sarcoma (KS) is an angioproliferative inflammatory condition that occurs commonly in patients infected with human immunodeficiency virus (HIV). Inflammatory cytokines and growth factors promote the development of KS. Because physiologically important cytokine polymorphisms modulate host inflammatory responses, we investigated the association between KS and common regulatory polymorphisms in 5 proinflammatory cytokine genes encoding interleukin (IL) IL-1alpha, IL-1beta, tumor necrosis factor (TNF) alpha, TNF-beta, and IL-6 and in the IL-1 receptor antagonist (IL1RN). We also examined the contribution of stromal-derived factor 1 and chemokine receptor 5 (Delta32) polymorphisms to KS development. The population consisted of 115 HIV-infected men with KS and 126 deceased HIV-infected men without KS. The only strong association was observed between an IL6 promoter polymorphism (G-174C) and susceptibility to KS in HIV-infected men (P =.0035). Homozygotes for IL6 allele G, associated with increased IL6 production, were overrepresented among patients with KS (P =.0046), whereas allele C homozygotes were underrepresented (P =.0062). Substantial in vitro evidence indicates that IL-6 contributes to the pathogenesis of KS. Our results show that IL6 promoter genotypes associated with altered gene expression are risk factors for development of KS. Identification of a genetic risk factor for development of KS has important clinical implications for prevention and therapy.

Alleles↗

PubMed2000

Fatal intoxication with melperone.

Melperone is judged to be a safe neuroleptic drug. Until now there has been no report of a melperone fatality, though it has been used in suicide attempts. We report on a case of a 36-year-old woman where no cause of death could be established at autopsy. Criminological investigation pointed to a homicide by poisoning but also the possibility of a suicide had to be taken in account. The toxicological analysis of blood, cerebral spinal fluid and urine revealed extremely high concentrations of melperone which had never been reported before. Furthermore, diazepam, nordazepam and carbamazepine were detected. To our knowledge, this case is the first melperone fatality. Possible interactions with diazepam and carbamazepine are discussed.

Adult↗

PubMed2000

Methadone-related fatalities in Hamburg 1990-1999: implications for quality standards in maintenance treatment?

Drug-related fatal poisonings were analysed in Hamburg from 1990 to 30th June 1999 with special attention to the role of methadone. The first methadone-related fatalities were observed in Hamburg three years after methadone maintenance treatment (MMT) was introduced in 1990. Meanwhile more than half of all fatal poisonings among drug addicts are monovalent or polydrug intoxications with evidence for methadone. From January 1997 until June 1999 methadone was the predominant cause of death in about 39% of all drug-related fatal poisonings while the proportion of mixed heroin/methadone intoxications was about 10%. The rising problem of methadone-related fatalities goes with a decline of monovalent heroin intoxications which decreased in the last 9 years from 60% to 11%. Sixty-five per cent of those who died of fatal methadone-related poisonings had no history of MMT (60% of those with methadone as predominant cause of death). Since take-home doses for up to 7 days are prescribed to the patient due to a change in the German Narcotics Act in 1998, the diversion of methadone into illegal markets may have been accelerated. This results in rising numbers of non-intentional methadone-related fatalities among addicts who have never been in MMT. The prerequisites for the prescription of take-home doses should be taken more serious. There is no doubt that MMT reduced the mortality rate among the great majority of patients in Hamburg but supreme efforts should be made to prevent or reduce fatal intoxications by methadone in the non-treatment group.

Analgesics, Opioid↗

PubMed2000

Structure and chromosomal localization of the human and mouse muscle fructose-1,6-bisphosphatase genes.

Mammalian skeletal muscle contains fructose-1,6-bisphosphatase (Fru-1,6-P(2)ase), a key enzyme of glyconeogenesis. We have shown previously that muscle Fru-1,6-P(2)ase is encoded by a gene different from that coding for the liver isoenzyme. Starting with genomic YAC libraries and based on the cDNA sequences of human and mouse muscle Fru-1,6-P(2)ases together with the known gene structures of two mammalian liver fructose-1,6-bisphosphatases, we have PCR-amplified and sequenced all functional parts of the human and mouse muscle fructose-1,6-bisphosphatase genes and determined their chromosomal localization. The human gene (FBP2), localized at chromosome 1p36.1-2, spans about 30 kb, while the mouse gene (Fbp2) at chromosome 13B3-C1 is more compact (about 21 kb). Intron lengths are only poorly conserved between the two genes, while intron number and positions are identical in all hitherto analyzed mammalian fructose-1,6-bisphosphatase isoenzyme genes. Transcriptional start sites were found to be located 97 and 95bp before the start codon in the human gene and 35 bp before the start codon in the mouse homolog. A comparison of the 5'-flanking sequences of the two genes revealed a 56% homology up to human bp -607 before the first transcriptional start point, while upstream of this region we found no similarity. The data presented in this paper provide a basis for further studies of the mechanism of expression regulation and the elucidation of the physiological role of the enzyme.

Animals↗

PubMed2000

Selection of continuous epitope sequences and their incorporation into poly(ethylene glycol)-peptide conjugates for use in serodiagnostic immunoassays: application to Lyme disease.

Continuous epitope sequences were selected from immunogenic Bb proteins by epitope mapping. The identified epitope sequences were synthesized by solid phase peptide synthesis and purified by high performance liquid chromatography. Each epitope was conjugated individually to a multifunctional poly(ethylene glycol) (PEG) carrier. The result PEG-peptide conjugates were used as antigens in ELISA for diagnosis of Lyme disease. The results showed that the defined epitope peptides were Lyme disease specific and could be used in a format of PEG-peptide conjugate as the antigen to achieve improved sensitivity and specificity.

Amino Acid Sequence↗

PubMed2000

The psychiatric interview in the emergency department.

Psychiatric assessment of patients in the emergency department requires a psychological and medical approach. Acute medical problems must be investigated immediately, before a more nuanced exploration of emotional, cognitive, and behavioral aspects of these patients is undertaken. A multidimensional, nonreductive description then guides the treatment and disposition of patients in the emergency department.

Diagnosis, Differential↗

PubMed2000

Multiple intraabdominal soft-tissue masses in a man awaiting liver transplantation: a case study and discussion.

An unusual cause of abdominal soft-tissue masses is accessory splenic tissue. The Tc-99m-sulfur colloid liver-spleen scan is a valuable adjunct in making this diagnosis. This report describes a 47-year-old man who had an abdominal magnetic resonance imaging (MRI) scan as part of a pretransplant evaluation and was found to have multiple soft-tissue masses in the posterior aspect of his abdomen. His history was pertinent for a traumatic rupture of the spleen at the age of 12 years, for which he required a splenectomy. He had no symptoms or physical findings to indicate a lymphoproliferative disorder or other malignant process. His peripheral blood smear was remarkable for the absence of Howell-Jolly bodies. The nuclear scan confirmed the presence of uptake in the soft-tissue masses seen on MRI scan. This finding supports our diagnosis of splenosis in a man with a history of traumatic splenic rupture as a child.

Humans↗

PubMed2000

Posthospitalization home health care use and changes in functional status in a Medicare population.

OBJECTIVE: The objective of this work was to estimate the effect of Medicare beneficiaries' use of home health care (HHC) for 6 months after hospital discharge on the change in functional status over a 1-year period beginning before hospitalization. DATA SOURCES AND STUDY SETTING: Data came from the Medicare Current Beneficiary Survey, which is a nationally representative sample of Medicare beneficiaries, in-person interview data, and Medicare claims for 1991 through 1994 for 2,127 nondisabled, community-dwelling, elderly Medicare beneficiaries who were hospitalized within 6 months of their annual in-person interviews. STUDY DESIGN: Econometric estimation with the instrumental variable method was used to correct for observational data bias, ie, the nonrandom allocation of discharged beneficiaries to the use of posthospitalization HHC. The analysis estimates a first-stage model of HHC use from which an instrumental variable estimate is constructed to estimate the effect on change in functional status. PRINCIPAL FINDINGS: The instrumental variable estimates suggest that HHC users experienced greater improvements in functional status than nonusers as measured by the change in a continuous scale based on the number and mix of activities of daily living and instrumental activities of daily living before and after hospitalization. The estimated improvement in functional status could be as large as 13% for a 10% increase in HHC use. In contrast, estimation with the observational data on HHC use implies that HHC users had poorer health outcomes. CONCLUSIONS: Adjusting for potential observational data bias is critical to obtaining estimates of the relationship between the use of posthospitalization HHC and the change in health before and after hospitalization. After adjustment, the results suggest that efforts to constrain Medicare's spending for HHC, as required by the Balanced Budget Act of 1997, may lead to poorer health outcomes for some beneficiaries.

Activities of Daily Living↗

PubMed2000

HLA-C expression on platelets: studies with an HLA-Cw1-specific human monoclonal antibody.

BACKGROUND AND OBJECTIVES: The expression of HLA-C on the surface of platelets is rarely studied due to the lack of proper alloantisera. We addressed this question using an IgM human monoclonal antibody directed against HLA-Cw1 (VP6G3). MATERIAL AND METHODS: Both flow cytometry and complement dependent cytotoxicity studies were used in the current analysis. RESULTS: The expression of the HLA-Cw1 antigen on platelets is lower than on peripheral blood lymphocytes as shown by flow cytometry. Variation in expression levels between individuals is also observed. Using this antibody in a complement-dependent cytotoxicity assay, we did not observe lysis using platelets as targets, whereas peripheral blood lymphocytes of the same blood donors were adequately lysed. CONCLUSIONS: These results confirm that platelets indeed express HLA-C. Furthermore, the results support the insignificant role of HLA-C in immunological platelet refractoriness.

Antibodies, Monoclonal↗

PubMed2000

Evaluation of botulinum toxin A therapy in children with adductor spasm by gross motor function measure.

Intramuscular injection of botulinum neurotoxin A is a relatively new method for treating spastic movement disorders in children. One major goal of any therapy for patients with movement disorders is to improve gross motor function. In this study, 18 patients with adductor spasm were treated with botulinum neurotoxin A. Treatment effect was determined with the Gross Motor Function Measure, a standardized, validated instrument designed to assist in assessment of gross motor function. Spastic muscle hyperactivity and joint mobility were evaluated by the modified Ashworth Scale and by range of motion, respectively. Compared to pretreatment values, significant improvement in gross motor function (P < .010), decrease in the modified Ashworth Scale, and increase in the range of motion (P < .010) were achieved. Patients with moderate impairment of gross motor function (classed at level III and level IV in the Gross Motor Function Classification System) benefited most from treatment. In patients with severe handicap (level V), only one of five treated patients showed improvement in gross motor function. Nevertheless, all patients in this subgroup benefited from improved ease in hygienic care. In conclusion, we have demonstrated that for most children with moderate functional impairment, the Gross Motor Function Measure is a useful instrument for objective documentation of improvements of gross motor function following treatment with botulinum neurotoxin A.

Adolescent↗

PubMed1999

A disulfide conjugate between anti-tetanus antibodies and HIV (37-72)Tat neutralizes tetanus toxin inside chromaffin cells.

Conjugates between anti-tetanus F(ab')2 fragments and the (37-72) fragment of the HIV Tat protein were taken up by chromaffin cells, NG108-15 neurohybridoma cells and Rev-2-T-6 lymphoma cells. The uptake could not be inhibited by competition with (37-72)Tat, but was reduced in the presence of metabolic inhibitors or at low temperature. The disulfide as well as the thioether conjugate were translocated to the cytoplasmic space, but only the disulfide conjugate moderately restored the stimulated transmitter release inhibited by tetanus toxin. Therefore, disulfide conjugates are more promising than thioethers for the neutralization of intracellular antigens. These conjugates provide new tools to study neuroprotection against bacterial neurotoxins.

Animals↗

PubMed1999

Slow deformation and lower seismic hazard at the new madrid seismic zone

Global Positioning System (GPS) measurements across the New Madrid seismic zone (NMSZ) in the central United States show little, if any, motion. These data are consistent with platewide continuous GPS data away from the NMSZ, which show no motion within uncertainties. Both these data and the frequency-magnitude relation for seismicity imply that had the largest shocks in the series of earthquakes that occurred in 1811 and 1812 been magnitude 8, their recurrence interval should well exceed 2500 years, longer than has been assumed. Alternatively, the largest 1811 and 1812 earthquakes and those in the paleoseismic record may have been much smaller than typically assumed. Hence, the hazard posed by great earthquakes in the NMSZ appears to be overestimated.

Journal Article↗

PubMed1999

Retropharyngeal abscess: an unusual complication of tracheal intubation.

A 42-year-old man presented as an emergency to the ENT department with sore throat and complete dysphagia, having undergone an umbilical hernia repair under general anaesthesia with tracheal intubation 3 weeks previously at another institution. One course of antibiotics from his general practitioner improved the symptoms but, on discontinuation of the antibiotics, symptoms flared up leading to complete dysphagia. Indirect laryngoscopy showed a bulging of the retropharyngeal wall, which was confirmed as a widening of the retropharyngeal space on a lateral soft-tissue X-ray film of the neck. Surgical exploration confirmed a retropharyngeal abscess, which probably occurred as a complication of the original tracheal intubation.

Adult↗

PubMed1999

Genotyping for human platelet-specific antigens HPA-1, -2, -3, -4 and -5 in the Slovenian population reveals a slightly increased frequency of HPA-1b and HPA-2b as compared to other European populations.

Typing of human platelet alloantigens (HPA) is necessary in various clinical situations. The purpose of this study was to type a random sample of the Slovenian population for HPA alleles, in order to obtain genetic population data. A total of 152 unrelated Slovenian blood donors were genotyped for HPA-1, -2, -3, -4 and -5 alleles using a simple method that enables simultaneous and complete determination of HPA genotypes. Ten different polymerase chain reactions employing sequence-specific priming (PCR-SSP), which worked in identical cycling conditions, were used. The allele frequencies were 0.809 for HPA-1a, 0.191 for HPA-1b, 0.891 for HPA-2a, 0.109 for HPA-2b, 0.591 for HPA-3a, 0.407 for HPA-3b, 0.997 for HPA-4a, 0.00 for HPA-4b, 0.934 for HPA-5a and 0.066 for HPA-5b. When compared to results of studies of various other Caucasian populations, our population displayed a slightly but not significantly higher proportion of the HPA-1b and 2b alleles.

Antigens, Human Platelet↗

PubMed1999

Translational effects of peptide antagonists of Tat protein of human immunodeficiency virus type 1.

The Tat (trans-activator of transcription) regulatory protein of human immunodeficiency virus (HIV-1) acts by interacting with the TAR RNA domain of nascent viral transcripts and with cellular proteins to increase viral transcription. In Jurkat-derived HCLE-D36 cells, which are stably transfected with the chloramphenicol acetyltransferase (CAT) reporter gene expressed from the TAR-encoding long terminal repeat (LTR) of HIV-1, CAT protein expression is dependent on Tat. The Tat9-K-biotin peptide antagonist of Tat binds specifically to TAR RNA and competes with Tat for binding. In the cellular expression system, Tat9-K-biotin reduces Tat-dependent CAT expression. However, while the Tat antagonist greatly reduces CAT protein production and polysome association of CAT mRNA, it has little effect on CAT mRNA levels, suggesting that the antagonist works at the post-transcriptional level.

Anti-HIV Agents↗

PubMed1999

Ectodermal patterning in the avian embryo: epidermis versus neural plate.

Ectodermal patterning of the chick embryo begins in the uterus and continues during gastrulation, when cells with a neural fate become restricted to the neural plate around the primitive streak, and cells fated to become the epidermis to the periphery. The prospective epidermis at early stages is characterized by the expression of the homeobox gene DLX5, which remains an epidermal marker during gastrulation and neurulation. Later, some DLX5-expressing cells become internalized into the ventral forebrain and the neural crest at the hindbrain level. We studied the mechanism of ectodermal patterning by transplantation of Hensen's nodes and prechordal plates. The DLX5 marker indicates that not only a neural plate, but also a surrounding epidermis is induced in such operations. Similar effects can be obtained with neural plate grafts. These experiments demonstrate that the induction of a DLX5-positive epidermis is triggered by the midline, and the effect is transferred via the neural plate to the periphery. By repeated extirpations of the endoderm we suppressed the formation of an endoderm/mesoderm layer under the epiblast. This led to the generation of epidermis, and to the inhibition of neuroepithelium in the naked ectoderm. This suggests a signal necessary for neural, but inhibitory for epidermal development, normally coming from the lower layers. Finally, we demonstrate that BMP4, as well as BMP2, is capable of inducing epidermal fate by distorting the epidermis-neural plate boundary. This, however, does not happen independently within the neural plate or outside the normal DLX5 domain. In the area opaca, the co-transplantation of a BMP4 bead with a node graft leads to the induction of DLX5, thus indicating the cooperation of two factors. We conclude that ectodermal patterning is achieved by signalling both from the midline and from the periphery, within the upper but also from the lower layers.

Animals↗

PubMed1999

Nuclear beta-catenin and the development of bilateral symmetry in normal and LiCl-exposed chick embryos.

Studies in Xenopus laevis and zebrafish suggest a key role for beta-catenin in the specification of the axis of bilateral symmetry. In these organisms, nuclear beta-catenin demarcates the dorsalizing centers. We have asked whether beta-catenin plays a comparable role in the chick embryo and how it is adapted to the particular developmental constraints of chick development. The first nuclear localization of beta-catenin is observed in late intrauterine stages of development in the periphery of the blastoderm, the developing area opaca and marginal zone. Obviously, this early, radially symmetric domain does not predict the future organizing center of the embryo. During further development, cells containing nuclear beta-catenin spread under the epiblast and form the secondary hypoblast. The onset of hypoblast formation thus demarcates the first bilateral symmetry in nuclear beta-catenin distribution. Lithium chloride exposure also causes ectopic nuclear localization of beta-catenin in cells of the epiblast in the area pellucida. Embryos treated before primitive streak formation become completely radialized, as shown by the expression of molecular markers, CMIX and GSC. Lithium treatments performed during early or medium streak stages cause excessive development of the anterior primitive streak, node and notochord, and lead to a degeneration of prospective ventral and posterior structures, as shown by the expression of the molecular markers GSC, CNOT1, BMP2 and Ch-Tbx6L. In summary, we found that in spite of remarkable spatiotemporal differences, beta-catenin acts in the chick in a manner similar to that in fish and amphibia.

Animals↗