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Biomedical subjects

J Stein

Publications and source records attributed to J Stein.

At least 37 records · Page 2Linked to original sources

Voriconazole-induced QT interval prolongation and ventricular tachycardia: a non-concentration-dependent adverse effect.

A 15-year-old patient with acute lymphoblastic leukemia and Fusarium infection was treated with voriconazole. She developed asymptomatic bradycardia, QT interval prolongation, and nonsustained, polymorphic ventricular tachycardia, which recurred upon rechallenge with the drug. Voriconazole levels and metabolism were within expected normal values. This non-concentration-dependent, voriconazole-associated ventricular tachycardia mandates cardiac rhythm monitoring during voriconazole treatment.

Adolescent↗

In vivo evaluation of a novel pH- and time-based multiunit colonic drug delivery system.

BACKGROUND: Targeted drug delivery to the colon is important for topical treatment of inflammatory bowel diseases. Established targeting systems predominantly focus on either pH- or time-dependent release, or bacterial degradation. AIM: To perform a three-phase, crossover design trial evaluating a novel combined pH- and time-based multiunit delivery system. METHODS: Twelve healthy male volunteers each received 200 mg of caffeine as either uncoated immediate release tablets, coated pellets with pH-dependent rapid release (EUDRAGIT FS 30D), and pellets with pH- and time-based release (inner layer EUDRAGIT RL/RS 30D; outer layer EUDRAGIT FS 30D). Orocecal transit time was measured using lactose-[13C]ureide. Serum concentrations of caffeine were measured by high-performance liquid chromatography. RESULTS: In contrast to the uncoated tablet, both coated systems reached the ileocecal region almost at the same time (3.19 +/- 0.71 and 3.33 +/- 0.81 h). Serum caffeine profiles were significantly prolonged for the pH and time delivery system compared with the pH-only based system (median tmax 12.0 vs. 5.5 h; P < 0.001). This was further reflected by a lower Cmax value and a lower area under the curve within 24 h after application. CONCLUSION: Compared with the conventional delivery systems, drug release from the new dosage form may offer a new dimension for the oral treatment of mid to distal ulcerative colitis.

Administration, Oral↗

[Nutrition and dietary treatment of chronic inflammatory bowel disease].

The relationships between nutrition and chronic inflammatory bowel disease (CIBD) range from a possible involvement in the etiopathogenesis of the disease to dietary intervention in the various disease stages. CIBDs are often associated with dietary depletion. Prevention and treatment of malnutrition are therefore obligatory elements of therapy. The following stepped dietary treatment strategy applies: dietary counseling, supplementary dietary drinks, feeding via a stomach tube, parenteral alimentation. In the case of uncomplicated CIBD, an adequate and balanced diet (light full diet) is the goal. In the event of malnutrition, during an acute attack, and when complications occur, the diet must be adapted accordingly. Total parenteral alimentation is, per se, more likely to be associated with complications, is more expensive that enteral alimentation, and is thus reserved for specific indications.

Adult↗

Tetraploid races of Paspalum notatum show polysomic inheritance and preferential chromosome pairing around the apospory-controlling locus.

The objective of this work was to determine the type of inheritance (disomic/polysomic) in tetraploid (2 n=4 x=40) Paspalum notatum and investigate the transmission pattern of the chromosome region associated with apospory. An F(1) family segregating for the reproductive mode (aposporous vs non-aposporous) was generated by crossing a tetraploid sexual plant as female parent with an apomictic individual as pollen donor. Pollen mother cells from both parental plants were examined to ascertain chromosome-pairing behavior at meiosis. The high rate of quadrivalent chromosome associations indicated an autotetraploid origin of the species, although bivalent pairing and occasional univalents were detected. The observation of a lagging bivalent, a bridge of chromatin, or two aligned laggards in the aposporous parent suggested a chromosome inversion in this strain. Segregation ratios of AFLP markers and the proportion of linkages in repulsion versus coupling phase denoted tetrasomic inheritance, but markers displaying disomic ratios were also observed. Preferential chromosome pairing (disomic inheritance) in the chromosome segment related to apospory was detected. The possible relationship between a chromosome rearrangement and the inheritance of apospory is discussed.

Alleles↗

Combining infliximab and methotrexate in fistulizing Crohn's disease resistant or intolerant to azathioprine.

BACKGROUND: Crohn's disease is complicated by fistulas in 20-40% of patients at some time during the course of their illness. Azathioprine has been reported to heal fistulas in 30-40% of cases. Long-lasting effects by the anti-tumour necrosis factor-alpha antibody infliximab most often require repeated infusions. Methotrexate has been shown to be an effective drug in maintaining remission in Crohn's disease. AIM: To evaluate the combination of infliximab and methotrexate as therapy for fistulas in patients with Crohn's disease. METHODS: Twelve consecutive patients (mean age, 29.5 years) with fistulizing Crohn's disease resistant or intolerant to azathioprine were followed prospectively. Patients received three infusions of infliximab (5 mg/kg) and long-term methotrexate (20 mg/week). Therapy success was defined as sustained closure of fistulas > or = 6 months after fistula closure. RESULTS: In four of the 12 patients, complete closure of fistulas that persisted for > or = 6 months (median follow-up, 13.25 months) was observed. In three further patients, a partial response was noted. In five patients, persistent therapy success could not be achieved or therapy had to be stopped due to side-effects. CONCLUSIONS: A combination of infliximab with long-term methotrexate may be a promising concept in fistulizing Crohn's disease. Our data indicate the need for larger controlled trials.

Adult↗

Tumor cells are present in stem cell harvests of Ewings sarcoma patients and their persistence following transplantation is associated with relapse.

BACKGROUND: Tumor cells frequently contaminate autologous stem cell products in a variety of malignancies, but their clinical significance remains controversial. We retrospectively monitored tumor contamination in stem cell harvests from patients with Ewing family of tumors (EFT) all harboring the specific translocation EWS-FLI-1 that characterize these tumors. PROCEDURE: Twenty- seven harvests from 11 patients were included in the study. In addition, 6 and 19 bone marrow (BM) or peripheral blood (PBL) samples were available before and after transplantation, respectively, for RT-PCR and nested PCR analyzes. RESULTS: All 11 patients had contaminating tumor cells in their harvests. All samples prior to transplantation were RT-PCR positive. Two out of the 11 patients who underwent transplantation died of complications. Out of the remaining nine patients, two are alive and well 68 and 84 months from diagnosis, and are the only patients with no detectable tumor cells in their samples after transplantation. One of these patients harbored contaminating tumor cells in only one of the two harvests collected. Seven patients relapsed after transplant, and in four patients BM/PBL samples were available prior to the clinical relapse. All these samples harbored contaminating tumor cells. CONCLUSIONS: We suggest a possible correlation between the amount of contaminating cells in the harvest and relapse after transplantation. Quantitative RT-PCR studies of the chimeric transcripts are underway to explore this issue.

Adolescent↗

[(13)C-breath tests for the assessment of liver function].

Routine work-up of hepatic diseases is performed by regular laboratory tests which indicate changes in the metabolic capacity of various hepatic cellular systems. A (13)C-based breath test may offer further selective characterisation of hepatic enzymes by means of a non-invasive technique. We present an overview on current test systems and their potential relevance in the assessment of hepatic diseases.

Breath Tests↗

A study for the evaluation of safety and tolerability of intravenous high-dose iron sucrose in patients with iron deficiency anemia due to gastrointestinal bleeding.

INTRODUCTION: The provision of adequate iron to support erythropoiesis in iron deficient patients is a time-consuming process which may present compliance problems for patients in the outpatient setting. The aim of the present study was to evaluate the safety and tolerability of intravenous high-dose iron sucrose therapy specifically in patients with iron deficiency anemia (IDA) due to gastrointestinal blood loss. METHODS: A single dose of iron sucrose of 7 mg iron/kg body weight (not exceeding 500 mg) was infused over 3.5 hours in 31 consecutive patients with IDA due to gastrointestinal blood loss. Safety and tolerability of the therapy was assessed by the occurrence of adverse events under therapy and up to one week after completion of the study. Further examinations comprised vital parameters, ECG, and clinical chemistry including iron indices. RESULTS: A total of 14 adverse events were observed in 10 patients, of which two adverse events in two patients were considered as being definitely related to drug administration. None of the patients had to be withdrawn from therapy. Significant changes in vital parameters and ECG during therapy and follow-up were not observed and clinical chemistry remained unchanged. DISCUSSION: A single intravenous high-dose iron sucrose therapy in patients with IDA due to gastrointestinal blood loss appears to be safe and therefore is a therapeutic option which may save time and improve patient compliance.

Adult↗

Enteral nutrition by endoscopic means; I. Techniques, indications, types of enteral feed.

Enteral nutritional support plays a major role in the management of patients who are critically ill in intensive care units (ICU), those with poor volitional intake, persons with chronic neurological or mechanical dysphagia, and individuals with gut dysfunction. Part I of this review will briefly discuss the principles governing nasoenteral feeding and will describe in detail the endoscopic-assisted methods for placing enteral feeding tubes. These include percutaneous endoscopic gastrostomy, jejunal extension through a percutaneous endoscopic gastrostomy or direct endoscopic jejunostomy, and the "one-step button". In addition, the types of enteral food with focus on disease-specific enteral diets will be discussed. Finally, the latest innovations in enteral feeding including immune-enhancing nutrients such as arginine, omega-3 fatty acids, glutamine, and nucleotides advocated for critically ill patients will be discussed. Questions regarding possible complications and long-term results of the various methods of enteral feeding will be discussed separately in part II.

Critical Care↗

Enteral Nutrition by Endoscopic Means; II. Complications and Management.

Despite the benefits and the widespread use of enteral and tube feeding (ETF) some patients experience complications, which can be divided in three categories: mechanical, e. g., tube blockage or removal; gastrointestinal, e. g., vomiting, diarrhea; and metabolic, e. g., re-feeding syndrome, hyperglycemia. The type and frequency of complications related to tube feeding varies considerably in accordance with the access to the intestinal tract (e. g., nasoenteric vs. percutaneous gastric vs. small bowel), the composition of the formula diet used, and the severity of the underlying disease. For example, tube-related complications have been reported to occur in 0-20 % and gastrointestinal complications in 8-65 % of patients during early postoperative feeding via a needle catheter jejunostomy (NCJ) using comparable techniques. The complication rate can be reduced by careful observance of guidelines on tube feeding including those related to food composition, administration rate, portion size, food temperature, and supervision of the patient. Gastrointestinal side effects (including diarrhea) are without doubt the most frequent.

Endoscopy, Gastrointestinal↗

A clinical and molecular study of a Bedouin family with dysmegakaryopoiesis, mild anemia, and neutropenia cured by bone marrow transplantation.

OBJECTIVES: Familial thrombocytopenia is a relatively rare and heterogeneous group of clinical and genetic syndromes of unknown etiology. Recently, mutations in a few hematopoietic transcription factors were implicated in dysmegakaryopoiesis with and without dyserythropoietic anemia. The aim of the present study was to describe the clinical and hematologic picture of members of a Bedouin family with severe congenital thrombocytopenia associated with neutropenia and anemia and to determine the possible involvement of hematopoietic transcription factor genes in their disease. PATIENTS AND METHODS: Four members of a Bedouin family presented with severe bleeding tendency, including intracranial hemorrhage in three. Three of the four were successfully treated with allogenic human leukocyte antigen (HLA)-matched bone marrow transplants. Measurements of serum erythropoietin and thrombopoietin levels, bone marrow electron microscopy, and megakaryocytic colony were grown for each patient in addition to DNA amplification and single-strand conformation polymorphism of each exon of the NF-E2, Fli-1, FOG-1, and Gfi-1b in genes. RESULTS: Bone marrow studies revealed dysmegakaryopoiesis and mild dyserythropoiesis. A low number of bone marrow megakaryocyte colony-forming units was found, as well as a slightly elevated serum thrombopoietin level. No mutation was identified in any of the transcription factor genes examined. CONCLUSIONS: A unique autosomal recessive bone marrow disorder with prominent involvement of megakaryocytes is described. Defects were not identified in transcription factors affecting the common myeloid progenitor.

Anemia↗

Are there HLA combinations typical supporting for or making resistant against aggressive and/or chronic periodontitis?

OBJECTIVE AND BACKGROUND: Human leukocyte antigens (HLA)/alleles have been considered as risk factors for periodontal disease. However, data from HLA associations is not consistent. Diversity of HLA antigen combinations and en bloc inherited HLA alleles (haplotypes), as known in systemic diseases, can be variable factors in disease association. Therefore, the aim of this study was to investigate the incidence of HLA homozygosities, heterozygosities and estimated haplotypes in German Caucasian groups with generalized aggressive (N = 50) and chronic (N = 102) periodontitis in comparison to control probands without periodontitis (N = 102). METHODS: HLA-A, -B, -Cw, -DRB1, -DRB3/4/5, -DQB1 typing was carried out using both serologic (microlymphocytotoxicity test) and genomic (PCR-SSP: PCR with sequence specific primers) techniques. Frequencies of all homozygosities, heterozygosities and haplotypes were determined in all patients and controls. RESULTS: In both patient groups, associations to HLA homozygosities and heterozygosities were found. Most striking was the significantly lower frequency of HLA-DRBblank* homozygosity (non-DRB3*/DRB4*/DRB5*) in chronic periodontitis (p < 0.05), whereas HLA-DRB1*15 : DRB5*(DR51) : DQB1*06 showed a slightly higher homozygosity rate in all patients. As the combination HLA-A*02,A*03 was significantly decreased in aggressive periodontitis (p < 0.05), HLA-A*01,A*03 heterozygosity was significantly lowered in chronic periodontitis (p < 0.05). Among others, the known positive associations for HLA-A*68/69 (A28) and HLA-DRB1*04 were confirmed by the haplotypes HLA-A*68/69 : Cw*07 : B*18 in aggressive periodontitis (p < 0.05) and HLA-Cw*08 : B*14 : DRB1*04 in chronic periodontitis (p < 0.05). CONCLUSION: The present study elucidates the variety of HLA associations and therefore the difficulty to assign single HLA markers to periodontal disease. Susceptibility/resistance of both aggressive and chronic periodontitis may rather be influenced by particular HLA marker combinations. Associated HLA haplotypes may be of further importance for unknown gene loci representing a part of the genetic background for periodontitis. The different associations in aggressive and chronic periodontitis indicate different susceptibility/resistance factors for both diseases.

Adult↗

[Nutrition].

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Adult↗