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Biomedical subjects

P Schwartz

Publications and source records attributed to P Schwartz.

At least 19 recordsLinked to original sources

T-cell lymphoma associated with natural killer-like T-cell reaction.

We report a case of T-cell lymphoma showing in the peripheral blood (PB) exclusively T-lymphocytes with suppresser T-cell preponderance and a high percentage of natural killer (NK) marker positive cells by flow cytometry. A T-cell receptor (TCR) gene analysis of the PB leukocytes demonstrated rearrangements of TCRalpha, TCRbeta, and TCRgamma genes. Therefore, the phenotype and genotype appeared to be consistent with an NK-like T-cell leukemia/lymphoma. However, when the PB lymphocytes were separated by size, it was found that 80% of NK marker positive cells were in the smaller cell population, while the neoplastic cells were in the large cell gate. A diagnosis of T-cell lymphoma with reactive NK-like T-cells was finally confirmed by demonstrating the presence of both large atypical lymphoid cells and large granular lymphocytes (LGL) on PB smears. Although immunoperoxidase stain of bone marrow and colon showed positive T-cell markers in the tumor cell population, cytoplasmic granules could not be identified in tissue sections and, thus, a distinction between T-cell lymphoma and NK-like T-cell lymphoma could not be made by light microscopy until NK markers were studied. CD57 was demonstrated immunohistochemically in small lymphocytes but not in the large tumor cells in the colon. Electron microscopy, however, demonstrated LGL reaction to the lymphoma cells in the colonic biopsy. NK-like T-cell lymphoma usually carries a poorer prognosis than peripheral T-cell lymphoma, thus the distinction of these neoplasms is important. This study emphasizes that T-cell lymphoma may cause an LGL reaction or proliferation. If the lymphoma cells were of the same size as LGL, flow cytometric studies may have misled the diagnosis to NK-like T-cell-lymphoma.

Aged

Histamine in human breast cancer.

BACKGROUND: Histamine inhibits lymphocyte function in vitro at concentrations of greater than 10(-6) mol/l. The aim of this study was to determine whether histamine concentrations in breast cancers were sufficient to produce an immunological effect. METHODS: Tumour and adjacent normal breast content of histamine was measured using a radioenzymatic assay in 29 patients having surgery for breast cancer. RESULTS: The median content of histamine in breast cancer tissue was 5.4 (range 0.9-27.3) microg/g (median concentration 4.5 x 10(-5) mol/l), and was significantly greater than that in adjacent breast tissue (P = 0.007). CONCLUSION: The concentration of histamine in breast cancer was sufficient to inhibit lymphocyte function and could be locally immunosuppressive.

Adult

Differential release of lipoteichoic and teichoic acids from Streptococcus pneumoniae as a result of exposure to beta-lactam antibiotics, rifamycins, trovafloxacin, and quinupristin-dalfopristin.

The release of lipoteichoic acid (LTA) and teichoic acid (TA) from a Streptococcus pneumoniae type 3 strain during exposure to ceftriaxone, meropenem, rifampin, rifabutin, quinupristin-dalfopristin, and trovafloxacin in tryptic soy broth was monitored by a newly developed enzyme-linked immunosorbent assay. At a concentration of 10 microg/ml, a rapid and intense release of LTA and TA occurred during exposure to ceftriaxone (3,248+/-1,688 ng/ml at 3 h and 3,827+/-2,133 ng/ml at 12 h) and meropenem (2,464+/-1,081 ng/ml at 3 h and 2,900+/-1,364 ng/ml at 12 h). Three hours after exposure to rifampin, rifabutin, quinupristin-dalfopristin, and trovafloxacin, mean LTA and TA concentrations of less than 460 ng/ml were observed (for each group, P < 0.01 versus the concentrations after exposure to ceftriaxone). After 12 h of treatment, the LTA and TA concentrations were 463+/-126 ng/ml after exposure to rifampin, 669+/-303 ng/ml after exposure to rifabutin, and 1,236+/-772 ng/ml after exposure to quinupristin-dalfopristin (for each group, P < 0.05 versus the concentrations after exposure to ceftriaxone) and 1,745+/-1,185 ng/ml after exposure to trovafloxacin (P = 0.12 versus the concentration after exposure to ceftriaxone). At 10 microg/ml, bactericidal antibacterial agents that do not primarily affect cell wall synthesis reduced the amount of LTA and TA released during their cidal action against S. pneumoniae in comparison with the amount released after exposure to beta-lactams. Larger quantities of LTA and TA were released after treatment with low concentrations (1x the MIC and 1x the minimum bactericidal concentration) than after no treatment for all antibacterial agents except the rifamycins. This does not support the concept of using a low first antibiotic dose to prevent the release of proinflammatory cell wall components.

Anti-Bacterial Agents

In-vitro differentiation of mature dendritic cells from human blood monocytes.

Representing the most potent antigen-presenting cells, dendritic cells (DC) can now be generated from human blood monocytes. We recently presented a novel protocol employing GM-CSF, IL-4, and IFN-gamma to differentiate monocyte-derived DC in vitro. Here, such cells are characterized in detail. Cells in culture exhibited both dendritic and veiled morphologies, the former being adherent and the latter suspended. Phenotypically, they were CD1a-/dim, CD11a+, CD11b++, CD11c+, CD14dim/-, CD16a-/dim, CD18+, CD32dim/-, CD33+, CD40+, CD45R0+, CD50+, CD54+, CD64-/dim, CD68+, CD71+, CD80dim, CD86+/++, MHC class I++/ , HLA-DR++/ , HLA-DP+, and HLA-DQ+. The DC stimulated a strong allogeneic T-cell response, and further evidence for their autologous antigen-specific stimulation is discussed. Although resembling a mature CD11c+ CD45R0+ blood DC subset identified earlier, their differentiation in the presence of the Th1 and Th2 cytokines IFN-gamma and IL-4 indicates that these DC may conform to mature mucosal DC.

Animals

Evaluation of in vitro release rate and in vivo absorption characteristics of four metoprolol tartrate immediate-release tablet formulations.

The purpose of this investigation was to examine the impact of formulation and process changes on dissolution and bioavailability/bioequivalency of metoprolol tartrate tablets manufactured using a high-shear granulation process. A half-factorial (2(4-1), Res IV) design was undertaken to study the selected formulation and processing variables during scale-up. Levels and ranges for excipients and processing changes studied represented level 2 or greater changes as indicated by the SUPAC-IR Guidance. Blend and tableting properties were evaluated. Changes in sodium starch glycolate and magnesium stearate levels, and the order of addition microcrystalline cellulose (intra- vs. extragranular) were significant only in affecting percent drug released (Q) in 5, 10, and 15 min. Statistical analysis of data showed no significant curvature. No interaction effects were found to be statistically significant. To examine the impact of formulation and processing variables on in vivo absorption, three batches were selected for a bioavailability study based on their dissolution profiles. Subjects received four metoprolol treatments (Lopressor, slow-, medium-, and fast-dissolving formulations) separated by 1 week according to a randomized crossover design. After an overnight fast, subjects were administered one tablet (100 mg), blood samples were collected over 24 hr and plasma samples were analyzed. The formulations were found to be bioequivalent with respect to the log Cmax and log AUC0-infinity. The results of this study suggest that: (i) bioavailability/bioequivalency studies may not be necessary for metoprolol tartrate and perhaps other class 1 drugs after level 2 type changes and (ii) in vitro dissolution tests may be used to show bioequivalence of metoprolol formulations with processing or formulation changes within the specified level 2 ranges for the equipment examined.

Adrenergic beta-Antagonists

Scanning electron microscopy of the zona pellucida of human oocytes during intracytoplasmic sperm injection (ICSI).

During intracytoplasmic sperm injection (ICSI) approximately 10% of all injected oocytes degenerate. The reason for this process is unknown. It has been speculated that the mechanical procedure of the insertion of the ICSI needle induces injuries to the zona pellucida which lead to the death of the cell. By scanning electron microscope (SEM), it could be shown that the surface structure of mature oocytes is extremely elastic so that the injection needle penetrates the zona pellucida without destroying the mesh-like or more compact surface. No tissue pieces or zona fragments were detectable. After a culture time of 15 min the penetration site on the zona was no longer easily visible. We believe that oocyte degeneration is not caused by the penetration of a glass needle into the ooplasm but by an injury to the meiotic spindle or by an excessive dose of fluid [polyvinylpyrrolidone (PVP) or medium] during sperm injection.

Elasticity

Tumors of the respiratory tract observed at the German Primate Center, 1978-1994.

Eight spontaneous pulmonary tumors (four bronchiolar tubular adenomas, two bronchiolar adenocarcinomas, two squamous-cell carcinomas) occurred in a total of 54 adult tree shrews (Tupaia belangeri) of the GPC colonies between 1978 and 1994. The adenomas and adenocarcinomas consisted of tubularly or trabecularly arranged cuboidal to cylindrical cells interspersed with some PAS-positive goblet cells, thus resembling the epithelial lining of respiratory bronchioles of tree shrews. The two squamous-cell carcinomas probably originated from the pulmonary alveoles. Three more pulmonary tumors (one small-cell carcinoma, one bronchial adenoma, one squamous-cell carcinoma) developed in 409 adult callitrichids of the GPC colonies during the same period, and one more bronchial adenoma was observed in a common marmoset (Callithrix jacchus) of another colony located in Göttingen. With regard to the adenomas and squamous-cell carcinomas, a similar cellular origin with the three shrews is assumed. The small-cell carcinoma possibly developed from the bronchial epithelium, provided a pathogenesis parallel to that of human small-cell carcinoma is suggested. Four of the tree shrew pulmonary adenomas/adenocarcinomas and the small-cell Ca were macroscopically visible as yellowish-grey nodules of 1 mm x 1 mm to 15 mm x 15 mm diameter, predominantly involving the main lobes (2 x right main lobes, 2 x left main lobes, 1 x all lobes). The pulmonary tumors of the other animals were below macroscopical detectability.

Adenocarcinoma

d-Cycloserine enhances implicit memory in Alzheimer patients.

We tested the ability of d-cycloserine, a partial glycine agonist acting at the N-methyl-D-aspartate (NMDA) receptor complex, to improve implicit memory in Alzheimer patients in a parallel-group, placebo-controlled, double-blind study. One-hundred eight patients with probable Alzheimer's disease of mild to moderate severity received d-cycloserine (5, 15, or 50 mg) or placebo twice daily for 10 weeks. We then evaluated their ability to identify perceptually degraded words, some of which were repeated over multiple trials across 3 days. Implicit memory performance of words repeated across trials was significantly enhanced for the patients who received 15 mg d-cycloserine compared with those who received placebo. These findings support development of NMDA receptor-mediated glutamatergic interventions for the treatment of Alzheimer-related memory disorders.

Aged

[Surgery in patients with organ transplants].

Patients after successful transplantation with immunosuppressive therapy form a "new circle of surgical patients" who can develop various surgical diseases, or injuries which bring about an inevitable urgent or planned surgical treatment. The authors present the results in three patients with transplanted organs (1993-1995) who were subdued to various surgical treatments. The first patient underwent a classical cholecystectomy, choledochotomy, and extraction of concrement from the choledochus after orthotopic transplantation of the heart. The second patient underwent transplantation of the kidneys precedingly to bilateral subtotal resection of both lobes of the thyroid gland due to marked bilateral nodal goitre intervening deeply retrosternally with a severe pressure syndrome on trachea and oesophagus. The immediate and long-term results were excellent. Orthotopic transplantation of the heart in the third patient preceded to intercostal drainage of the thorax and evacuation of pus due to an extensive empyema of the thorax and septic state, and later thoracotomy and decortication with extirpation of the substantial part of the empyema sack was performed with an excellent immediate and long-term effect. The authors present the principles which must be inevitably fulfilled in coincidence with successive surgical treatment in patients with transplanted organs in a permanent immunocomplex regime. (Fig 2, Ref. 11.)

Adult

Quantitative in vivo 1H nuclear magnetic resonance spectroscopic imaging of neuronal loss in rat brain.

The aim of this research was to determine whether in vivo nuclear magnetic resonance spectroscopic measurement of N-acetyl aspartate, a neuron specific brain marker, provides a quantitative index of neuronal loss. Five rats were injected unilaterally in the corpus striatum with kainic acid, an analogue of glutamate that causes excitotoxic degeneration of intrinsic neurons, and were subjected to nuclear magnetic resonance imaging and spectroscopic imaging. Measurements of N-acetyl aspartate were determined in vivo and compared to post mortem nuclear magnetic resonance spectroscopic measures of N-acetyl aspartate and choline acetyl transferase and glutamate decarboxylase activities, biochemical markers for striatal intrinsic neuronal integrity. Mean per cent neuronal survival of hemispheres with lesion versus the contralateral hemispheres measured 72 for glutamate decarboxylase and 71 for N-acetyl aspartate (in vivo), 74 for N-acetyl aspartate (in vitro), and 62 for choline acetyl transferase, respectively. Our studies in rats have shown that estimates of neuronal loss through nuclear magnetic resonance spectroscopic measurements of N-acetyl aspartate are equivalent to traditional neuronal enzyme activity assays. The results unequivocally demonstrate that N-acetyl aspartate is a valid and sensitive neuronal marker with the capability of providing accurate assessments of neuronal loss in vivo.

Animals

HEp-2 cell-adherent Escherichia coli in patients with human immunodeficiency virus-associated diarrhea.

Diarrhea occurs commonly in African human immunodeficiency virus (HIV) infections. A case-control (HIV-positive vs. -negative) study of adults with diarrhea was done in Lusaka, Zambia, to determine the prevalence of intestinal infection by HEp-2 cell-adherent Escherichia coli. Adherent E. coli were more common in HIV-positive patients with acute diarrhea than among HIV-negative controls (60% vs. 33%) and were found significantly more often in HIV-positive patients with chronic diarrhea than among HIV-negative controls with chronic diarrhea (79% vs. 17%, P < .002). Adherent strains were found significantly more often among HIV-positive patients (69%) than in 22 asymptomatic subjects (36%, P < .02). The HEp-2 cell adherence of the E. coli strains did not show a common pattern. Adherent bacteria were also observed in colonic biopsies from 32% of Zambians with chronic diarrhea who underwent endoscopy. Adherent E. coli may be an important cause of HIV-associated diarrhea in Zambia.

Acute Disease

Clinical stage I endometrial carcinoma: pitfalls in preoperative assessment with MR imaging. Work in progress.

PURPOSE: To identify potential pitfalls in using magnetic resonance (MR) imaging to determine the depth of myometrial invasion in patients with clinical stage I endometrial carcinoma. MATERIALS AND METHODS: Forty women with clinical stage I endometrial carcinoma underwent preoperative pelvic MR imaging. Uterine length, tumor signal intensity, appearance of the junctional zone, presence of large polypoid tumors, leiomyomata, and congenital uterine anomalies were analyzed. Univariate logistic-regression analysis was performed to identify associations between incorrect MR staging and these variables. RESULTS: MR staging of IA, IB, and IC disease was 55% accurate (22 of 40 cases); MR differentiation of deep myometrial invasion (stage IC) from superficial disease (stages IA and IB) was 78% accurate (31 of 40 cases). Older age (P = .025), presence of polypoid tumors (P = .025), and difficulty in pathologic staging (P < .005) were significantly associated with incorrect MR assessment. CONCLUSION: When present, large polypoid tumors, leiomyomata, congenital anomalies, small uteri, and indistinct zonal anatomy may make it difficult to assess myometrial invasion at MR imaging.

Aged

Evaluation of cycloserine in the treatment of Alzheimer's disease.

This multicenter study evaluated the efficacy and safety of cycloserine and measured its effects on explicit and implicit memory tests in patients with Alzheimer's disease (AD). Four hundred ten patients with AD, aged 50 years or older, were enrolled in this parallel-group, double-blind, placebo-controlled, randomized trial of 5, 15, or 50 mg cycloserine or placebo twice daily, and 403 entered the double-blind treatment phase. Two hundred sixty-five patients completed the entire 26-week treatment phase. There were no baseline differences among the four treatment groups. Cognitive Drug Research (CDR) efficacy assessments showed no differences between active treatments and placebo from baseline to study weeks 2, 6, 14, or 26. Patients receiving 15 mg of cycloserine improved significantly on one section of an implicit memory test. No differences among treatments were observed for any other assessment scales evaluated. The incidence and severity of adverse events were similar across treatment groups. Cycloserine was well tolerated but did not demonstrate consistent evidence of efficacy during the course of therapy. Higher doses may be necessary to achieve efficacy in the AD population and do not appear to be precluded by the adverse event profile seen in this study.

Aged

[Latent hypothyroidism--a minor laboratory variation or a disease?].

Latent hypothyreosis is a state which is characteristic by normal values of thyroid hormones (T3, T4) and moderately increased values of thyroid-stimulating hormone (TSH), or extensive response of TSH after stimulation with thyrotrophin-releasing hormone (TRH-test). The characteristic symptoms include goitre, symptoms of mammary glands (galactorrhea, benign mammary dysplasia), impairment of menstruation cycle and fertility and psychic disturbances (depressive symptomatology, deterioration of memory). The characteristic laboratory alterations include increased basal or stimulated values of prolactin and impairment of lipoprotein metabolism (significant decrease of HDL, increase of LDL). This aspect often makes the indication of substitution therapy justified in spite of normal concentrations of peripheral hormones. (Ref. 26).

Humans