Biomedical subjects
A Stein
Publications and source records attributed to A Stein.
[Acrocyanosis: crucial symptom in a case of chronic diarrhea and weight loss].
The patient reported here was admitted because of severe dehydration caused by watery diarrhea. As underlying disease we found bacterial overgrowth of the small bowel due to myopathic dysmotility of the small bowel as a manifestation of CREST syndrome. An important clue to the diagnosis was the result of a ward round: the patient showed Raynaud's phenomenon when exposed to the cold at an open window airing the room. A leading tool for diagnosis and therapy proved to be small bowel manometry which is further discussed in this case report.
A long-term follow-up report on allogeneic stem cell transplantation for patients with primary refractory acute myelogenous leukemia: impact of cytogenetic characteristics on transplantation outcome.
The prognosis of patients with primary refractory acute myelogenous leukemia (AML) is poor. Our initial report suggested that some patients could achieve durable remission after allogeneic stem cell transplantation (SCT). Herein, we update our initial experience and report further analysis of this group of patients to determine whether there are pre-SCT prognostic factors predictive of posttransplantation relapse and survival. We reviewed the records of 68 patients who consecutively underwent transplantation at the City of Hope Cancer Center with allogeneic SCT for primary refractory AML between July 1978 and August 2000. Potential factors associated with overall survival and disease-free survival were examined. With a median follow-up of 3 years, the 3-year cumulative probabilities of disease-free survival (DFS), overall survival (OS), and relapse rate for all 68 patients were 31% (95% confidence interval [CI], 20%-42%), 30% (95% CI, 18%-41%), and 51% (95% CI, 38%-65%), respectively. In multivariate analysis, the only variables associated with shortened OS and DFS included the use of an unrelated donor as the stem cell source (relative risk, 2.23 [OS] and 2.05 [DFS]; P =.0005 and.0014, respectively) and unfavorable cytogenetics before SCT (relative risk: 1.68 [OS] and 1.58 [DFS]; P =.0107 and.0038, respectively). Allogeneic SCT can cure approximately one third of patients with primary refractory AML. Cytogenetic characteristics before SCT correlate with transplantation outcome and posttransplantation relapse.
Reduced-intensity allogeneic stem cell transplantation for patients whose prior autologous stem cell transplantation for hematologic malignancy failed.
Autologous hematopoietic stem cell transplantation (autoSCT) is an effective treatment for patients with various hematologic malignancies. Despite the significant improvement in the overall outcome, disease progression after transplantation remains the major cause of treatment failure. With longer follow-up, therapy-related myelodysplasia/acute myelogenous leukemia is becoming an important cause of treatment failure. The prognosis for these 2 groups of patients is very poor. Allogeneic hematopoietic stem cell transplantation (alloSCT) is a potential curative treatment for these patients. However, the outcome with conventional myeloablative alloSCT after failed autoSCT is typically poor because of high transplant-related mortality. In an attempt to reduce the treatment-related toxicity, we studied a reduced-intensity conditioning regimen followed by alloSCT for patients with progressive disease or therapy-related myelodysplasia/acute myelogenous leukemia after autoSCT. This report describes the outcomes of 28 patients with hematologic malignancies who received a reduced-intensity alloSCT after having treatment failure with a conventional autoSCT. Fourteen patients received a hematopoietic stem cell transplant from a related donor and 14 from an unrelated donor. The conditioning regimen consisted of low-dose (2 Gy) total body irradiation with or without fludarabine in 4 patients and the combination of melphalan (140 mg/m(2)) and fludarabine in 24. Cyclosporine and mycophenolate mofetil were used for posttransplantation immunosuppressive therapy, as well as graft-versus-host disease (GVHD) prophylaxis, in all patients. All patients engrafted and had >90% donor chimerism on day 100 after SCT. Currently, 13 patients (46%) are alive and disease free, 7 patients (25%) developed disease progression after alloSCT, and 8 (32%) died of nonrelapse causes. Day 100 mortality and nonrelapse mortality were 25% and 21%, respectively. With a median follow-up of 24 months for surviving patients, the 2-year probabilities of overall survival, event-free survival, and relapse rates were 56.5%, 41%, and 41.9%, respectively. Six patients (21%) developed grade III to IV acute GVHD. Among 21 evaluable patients, 15 (67%) developed chronic GVHD. We conclude that (1) reduced-intensity alloSCT is feasible and has an acceptable toxicity profile in patients who have previously received autoSCT and that (2) although follow-up was short, a durable remission may be achieved in some patients who would otherwise be expected to have a poor outcome.
Children's representation of family mealtime in the context of maternal eating disorders.
BACKGROUND: Recent research provides evidence for specific disturbance in feeding and growth in children of mothers with eating disorders. AIM: To investigate the impact of maternal eating disorders during the post-natal year on the internal world of children, as expressed in children's representations of self and their mother in pretend mealtime play at 5 years of age. METHODS: Children of mothers with eating disorders (n = 33) and a comparison group (n = 24) were videotaped enacting a family mealtime in pretend play. Specific classes of children's play representations were coded blind to group membership. Univariate analyses compared the groups on representations of mother and self. Logistic regression explored factors predicting pretend play representations. RESULTS: Positive representations of the mother expressed as feeding, eating or body shape themes were more frequent in the index group. There were no other significant group differences in representations. In a logistic regression analysis, current maternal eating psychopathology was the principal predictor of these positive maternal representations. Marital criticism was associated with negative representations of the mother. CONCLUSIONS: These findings suggest that maternal eating disorders may influence the development of a child's internal world, such that they are more preoccupied with maternal eating concerns. However, more extensive research on larger samples is required to replicate these preliminary findings.
Pneumococcal meningitis in an immunocompetent adult with a cochlear implant.
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Circle ligation of in vitro assembled chromatin indicates a highly flexible structure.
Evidence is provided that some condensed linker histone-containing chromatin structures are highly flexible in solutions containing 2 mM Mg2+. Chromatin assembled in vitro +/- histone H5 on a 6.3 kb linear DNA fragment in 90 mM NaCl using the polyglutamic acid method sedimented fairly homogeneously. The H5-containing sample had s(20, w) values that were 58-69% greater than the sample lacking H5. Chromatin assembled on linear pUC19 plasmid DNA was treated with T4 DNA ligase in solutions containing 2 mM Mg2+ over a range of DNA concentrations. It was found that the intramolecular DNA ends of the chromatin could be joined together more efficiently than the intramolecular ends of the naked DNA at the higher DNA concentrations. This result could not be attributed to the effective reduction in DNA length by nucleosome formation. The chromatin structures formed did not have naked DNA tails extending from the ends as assessed by exonuclease III digestion. Chromatin assembled on DNA shortened by up to 420 bp gave very similar results, suggesting that the structure was a flexible one, rather than a rigid one having DNA ends that were fortuitously juxtaposed.
Quantification of antigen-reactive T cells by a modified ELISPOT assay based on freshly isolated blood dendritic cells.
The enzyme-linked immunospot (ELISPOT) assay has become a widely employed method for quantification of antigen-reactive T lymphocytes. In recent years, various types of antigen-presenting cells (APCs) have been tested as stimulator cells in ELISPOT protocols to achieve a highly sensitive and rapid assay which is not impaired by a marked nonspecific cytokine release. However, the currently available APCs still have disadvantages, such as significant background reactivities, limited sensitivity, and time-consuming preparation procedures. Recently, we succeeded in defining a novel subpopulation of circulating dendritic cells (DCs) that can easily be prepared from human blood. These M-DC8+ DCs proved to be very effective in the induction of antigen-specific T cell responses. In the present study we provide evidence that M-DC8+ DCs are particularly well suited as APCs for the detection of antigen-specific CD8+ T cells after challenge with viral or tumor peptides in ELISPOT assays. In addition, protein-loaded M-DC8+ DCs proved to be quite efficient in the presentation of MHC class II-bound peptides, thus allowing the determination of frequencies of antigen-reactive CD4+ T cells. The use of M-DC8+ DCs as stimulator cells can improve the ELISPOT assay by combining high sensitivity, rapidity, and low background reactivity.
[Initial scleromyxedema. Successful treatment with melphalan].
Scleromyxedema is a rare mucinous disease without thyroid dysfunction, associated with a monoclonal gammopathy. The deposits of mucin in the skin and other organs such as the cardiovasculary system, determine the prognosis of the disease. A 74-year old patient with initial scleromyxedema is described, in whom a pulse therapy with melphalan was initiated already in the early stages of the disease. Four cycles of melphalan in combination with prednisolon led to a complete and sofar stable remission of the disease.
[Multiple miliary osteomas of the face].
Osteoma cutis is a single or multiple ectope calcification with development of bony structures in the skin. We distinguish between primary and secondary ossification. Multiple miliary osteoma in the face has mostly been described secondary to preexisting acne vulgaris. We present a 62-year-old woman who developed multiple miliary osteoma in the face together with repeated doses of estrogen and discuss pathogenesis and therapeutic possibilities.
CD26 expression and enzymatic activity in recipients of kidney allografts.
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Cytotoxic phenotype of intra-epithelial lymphocytes in normal and cryptorchid human testicular excurrent ducts.
BACKGROUND: Most testicular and epididymal lymphocytes express T-cell markers, but their cytotoxic potential and activation status have not been reported. In this study, distribution of the cytotoxic cells was compared between normal and cryptorchid testes stratified into two groups: the first with complete absence of germ cells [Sertoli cell-only (SCO)] and the second with arrested spermatogenesis (SCA). METHODS: Immunohistochemistry for the T-lymphocyte marker CD3 and cytotoxic markers CD8, TIA-1 and granzyme B was performed on paraffin-embedded sections. RESULTS: The number of CD8+ and CD3+ intra-epithelial lymphocytes (IELs) increased distally throughout the normal epididymis. TIA-1 immunostaining revealed that a significant proportion of IELs exhibited cytotoxic potential, whereas granzyme B staining disclosed a subpopulation of activated cytotoxic lymphocytes (CTLs). TIA-1/CD8 and granzyme B/CD8 double immunostaining revealed that the vast majority of TIA-1+ and granzyme B+ cells were CD8+. The proportion of activated granzyme B+ lymphocytes increased distally throughout the normal epididymis. The number of TIA-1+ and granzyme B+ intra-epithelial and stromal lymphocytes was significantly increased in the normal as opposed to the SCO cryptorchid epididymis and proximal vas deferens. CONCLUSIONS: These results suggest that exposure of the testicular excurrent ducts to spermatozoa or immature germ cells triggers the activation and recruitment of CTLs. Cytotoxic granule effector mechanisms may contribute to the immunological barrier preventing the immune response to spermatozoa in testicular ducts.
The mental health of refugee children.
The UK is facing a major increase in the number of people seeking asylum each year, of whom approximately a quarter are children. The stressors to which refugees are exposed are described in three stages: (1) while in their country of origin; (2) during their flight to safety; and (3) when having to settle in a country of refuge. The evidence concerning the impact of displacement on children's mental health is reviewed and a framework for conceptualising the risk factors is proposed. The available literature shows consistently increased levels of psychological morbidity among refugee children, especially post-traumatic stress disorder, depression, and anxiety disorders. The principles underlying the delivery of mental health care for these children are also considered. It is argued that much primary prevention can be undertaken in the school context. Some key aspects of British immigration law are examined and the tension between the law and the best interests of the child principle is discussed. There is particular concern for the plight of unaccompanied children. Attention to the mental health needs of this vulnerable group is urgently required.
Synthesis and characterization of 2D and 3D structures from organic derivatives of polyoxometalate clusters: role of organic moiety, counterion, and solvent.
New organic derivatives of "inverse-Keggin" polyoxometalate (POM) clusters, [Mo(12)O(46)(AsR)(4)](4-) (R = C(6)H(4)-4-COOH, C(6)H(3)-4-OH-3-NO(2), C(6)H(4)-4-OH), have been synthesized. Structures of the corresponding sodium or iron salts were elucidated by single-crystal X-ray diffraction and shown to be 3D structures connected through hydrogen bonds and/or O-Na-O linkages. Parameters which influence the final solid-state architecture, such as the crystallizing solvent, organic moiety, and counterions, have been examined. The hydrogen-bonding ability of the solvent affects the connectivity of the POM clusters through interactions with the organic group and the inorganic core. The organic groups influence the structure through hydrogen bonds to other organic groups, to neighboring clusters, and/or to solvent molecules. Hydrogen bonding between the organic groups and the solvent appears to inhibit some possible connectivity patterns, such as the hydrogen-bonded dimerization of carboxylic acid groups. Na(+) ions were found directly bonded to the cluster oxo ligands and provided linkages between clusters. Larger cations, such as transition metals, did not show this interaction, and other bonding methods dominated.
Trimethoprim-sulfamethoxazole (TMP-SMZ) dose escalation versus direct rechallenge for Pneumocystis Carinii pneumonia prophylaxis in human immunodeficiency virus-infected patients with previous adverse reaction to TMP-SMZ.
Trimethoprim-sulfamethoxazole (TMP-SMZ) is the most effective Pneumocystis carinii pneumonia (PCP) prophylactic agent, but adverse reactions are common among human immunodeficiency virus (HIV)-infected patients and limit its use. This randomized, double-blind controlled trial compared 2 methods of TMP-SMZ reintroduction, 6-day dose escalation and direct rechallenge, for PCP prophylaxis in HIV-infected patients who had experienced previous treatment-limiting reactions. The primary end point was the ability to take single-strength TMP-SMZ daily for 6 months. Seventy-five percent of the dose-escalation group and 57% of the direct-rechallenge group continued to receive daily single-strength TMP-SMZ for 6 months (P= .014). Among premature discontinuations, 58% of the dose-escalation group and 70% of the direct-rechallenge group were due to adverse reactions. None of these reactions was serious. This study provides evidence that it is possible to successfully reintroduce TMP-SMZ to a significant proportion of HIV-infected patients who have experienced mild-to-moderate treatment-limiting adverse reactions.
Prevalence of HIV-1 drug resistance in antiretroviral-naive patients: a prospective study.
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Surface modification of mesoporous, macroporous, and amorphous silica with catalytically active polyoxometalate clusters.
Transition-metal-substituted polyoxometalates (TMSP) of the type [MII(H2O)PW11O39]5- (M = Co, Zn) and [SiW9O37(CoII(H2O))3]10- have been chemically anchored to modified macroporous (400 nm pores), mesoporous (2.8 nm pores), and amorphous silica surfaces. The materials were characterized by solid-state 31P MAS NMR, UV-vis, FT-IR spectroscopy, and N2 adsorption experiments to verify cluster attachment and the structure of the TMSP on the support. On the basis of the spectroscopic evidence, clusters were attached datively to the surface, and the integrity of the [CoPW11] cluster was maintained for nonaqueous impregnation with TBA5[CoPW11]; partial degradation of the cluster occurred when it was impregnated from aqueous solution using the K5[CoPW11] salt. Both the amine surface groups and the cobalt centers in the clusters were found to be necessary to prevent cluster loss during washing or reaction processes. The catalytic activities of the supported TMSP clusters were tested by the epoxidation of cyclohexene to cyclohexene oxide in the presence of isobutyraldehyde. The percent conversion of the substrate and the amount of product formed per unit time were similar for [CoPW11] clusters on each of the three silica supports, but slightly lower than for purely homogeneous reactions. [SiW9Co3] clusters with three available cobalt centers exhibited higher catalytic activity with nearly identical performance on a silica support or in homogeneous solution.
Solid cancers after bone marrow transplantation.
PURPOSE: To evaluate the incidence and associated risk factors of solid cancers after bone marrow transplantation (BMT). PATIENTS AND METHODS: We analyzed 2,129 patients who had undergone BMT for hematologic malignancies at the City of Hope National Medical Center between 1976 and 1998. A retrospective cohort and nested case-control study design were used to evaluate the role of pretransplantation therapeutic exposures and transplant conditioning regimens. RESULTS: Twenty-nine patients developed solid cancers after BMT, which represents a two-fold increase in risk compared with a comparable normal population. The estimated cumulative probability (+/- SE) for development of a solid cancer was 6.1% +/- 1.6% at 10 years. The risk was significantly elevated for liver cancer (standardized incidence ratio [SIR], 27.7; 95% confidence interval [CI], 1.9 to 57.3), cancer of the oral cavity (SIR, 17.4; 95% CI, 6.3 to 34.1), and cervical cancer (SIR, 13.3; 95% CI, 3.5 to 29.6). Each of the two patients with liver cancer had a history of chronic hepatitis C infection. All six patients with squamous cell carcinoma of the skin had chronic graft-versus-host disease. The risk was significantly higher for survivors who were younger than 34 years of age at time of BMT (SIR, 5.3; 95% CI, 2.7 to 8.6). Cancers of the thyroid gland, liver, and oral cavity occurred primarily among patients who received total-body irradiation. CONCLUSION: The risk of radiation-associated solid tumor development after BMT is likely to increase with longer follow-up. This underscores the importance of close monitoring of patients who undergo BMT.