1/20. Scopulariopsosis and hypersensitivity pneumonitis in an addict.Granulomatosis caused by fungal spores of a soil saprophyte is a newly recognized pulmonary complication of intravenous drug addiction. Brown, non-budding spores were histologically identified in necrotic tissue, inside giant cells of sarcoidlike granulomata, and in the vicinity of focal angiitic lesions. The fungus was identified by culture as the dematiaceous scopulariopsis brumptii. Cultural and histopathologic studies of lung biopsy specimens established the diagnosis. We showed precipitating antibodies to fungal antigen in the serum, prepared from the patient's isolate. Similar granulomatous pulmonary lesions were experimentally produced in mice by a single intravenous injection of spores of S. brumptii. The spores remained viable but did not show evidence of growth in the animal's tissue. Precipitating antibodies to fungal antigen and immediate wheal and late necrotizing type of skin reactions were shown in the challenged mice. The studies support the notion that pulmonary hypersensitivity to fungal spores was mediated by an Arthus'-type phenomenon.- - - - - - - - - - ranking = 1keywords = sensitivity (Clic here for more details about this article) |
2/20. Analysis of p53 inactivation in a human T-cell leukemia virus type 1 Tax transgenic mouse model.Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia/lymphoma (ATLL). The HTLV-1 Tax protein has been strongly linked to oncogenesis and is considered to be the transforming protein of this virus. A Tax transgenic mouse model was utilized to study the contribution of p53 inactivation to Tax-mediated tumorigenesis. These mice develop primary, peripheral tumors consisting of large granular lymphocytic (LGL) cells, which also infiltrate the lymph nodes, bone marrow, spleen, liver, and lungs. Primary Tax-induced tumors and tumor-derived cell lines exhibited functional inactivation of the p53 apoptotic pathway; such tumors and tumor cell lines were resistant to an apoptosis-inducing stimulus. In contrast, p53 mutations in tumors were found to be associated with secondary organ infiltration. Three of four identified mutations inhibited transactivation and apoptosis induction activities in vitro. Furthermore, experiments which involved mating Tax transgenic mice with p53-deficient mice demonstrated minimal acceleration in initial tumor formation, but significantly accelerated disease progression and death in mice heterozygous for p53. These studies suggest that functional inactivation of p53 by HTLV-1 Tax, whether by mutation or another mechanism, is not critical for initial tumor formation, but contributes to late-stage tumor progression.- - - - - - - - - - ranking = 0.0070522589521193keywords = contrast (Clic here for more details about this article) |
3/20. Antibody response to IR6, a conserved immunodominant region of the VlsE lipoprotein, wanes rapidly after antibiotic treatment of borrelia burgdorferi infection in experimental animals and in humans.Invariable region (IR)(6), an immunodominant conserved region of VlsE, the antigenic variation protein of borrelia burgdorferi, is currently used for the serologic diagnosis of lyme disease in humans and canines. A longitudinal assessment of anti-IR(6) antibody levels in B. burgdorferi-infected rhesus monkeys revealed that this level diminished sharply after antibiotic treatment (within 25 weeks). In contrast, antibody levels to P39 and to whole-cell antigen extracts of B. burgdorferi either remained unchanged or diminished less. A longitudinal analysis in dogs yielded similar results. In humans, the anti-IR(6) antibody titer diminished by a factor of > or =4 in successfully treated patients and by a factor of <4 in treatment-resistant patients. This result suggests that the quantification of anti-IR(6) antibody titer as a function of time should be investigated further as a test to assess response to lyme disease therapy or to determine whether a B. burgdorferi infection has been eliminated.- - - - - - - - - - ranking = 0.0070522589521193keywords = contrast (Clic here for more details about this article) |
4/20. A neuroendocrine/small cell prostate carcinoma xenograft-LuCaP 49.The late stages of progression of prostate carcinoma are typically characterized by an androgen-insensitive, rapidly proliferative state. Some late-stage tumors are composed predominantly of neuroendocrine cells. Virtually no animal models of a neuroendocrine/small cell variant of prostate carcinoma are available for experimental studies. We report a human neuroendocrine/small cell prostate carcinoma xenograft that was developed from a nodal metastasis of a human prostate carcinoma and that has been propagated as serial subcutaneous implants in severe combined immunodeficient mice for >4 years. Designated LuCaP 49, all tumor passages exhibit a neuroendocrine/small cell carcinoma phenotype-insensitivity to androgen deprivation, expression of neuroendocrine proteins, lack of expression of prostate-specific antigen or androgen receptor, and an unusually rapid growth (a doubling time of 6.5 days) for prostate cancer xenografts. Genetically this tumor exhibits loss of heterozygosity for the short arm of chromosome 8 and has a complex karyotype. This xenograft should prove to be useful in the investigation of mechanisms underlying the androgen-insensitive state of progressive prostate carcinoma.- - - - - - - - - - ranking = 0.2keywords = sensitivity (Clic here for more details about this article) |
5/20. Iron-mobilizing properties of the gadolinium-DTPA complex: clinical and experimental observations.BACKGROUND: gadolinium (Gd) magnetic resonance imaging (MRI) contrast agents are considered to be safe in patients with impaired renal function. Our study investigates a mechanism of severe iron intoxication with life-threatening serum iron levels in a haemodialysis patient following MRI with Gd-diethylenetriaminepentaacetic acid (Gd-DTPA) administration. His previous history was remarkable for multiple blood transfusions and biochemical evidence of iron overload. We hypothesized that Gd-DTPA may have an iron-mobilizing effect in specific conditions of iron overload combined with prolonged exposure to the agent. methods: For the in vitro study, Gd-DTPA was added to mice liver homogenate and iron metabolism parameters were measured after incubation in comparison with the same samples incubated with saline only. For the in vivo study, an experimental model of acute renal failure in iron-overloaded rats was designed. Previously iron-overloaded and normally fed rats underwent bilateral nephrectomy by renal pedicle ligation, followed by Gd-DTPA or saline injection. Iron and iron saturation levels were checked before and 24 h after Gd-DTPA or vehicle administration. RESULTS: Significant mobilization of iron from mice liver tissue homogenate in mixtures with Gd in vitro was seen in the control (saline) and in the experimental (Gd) groups (513 /-99.1 vs 1117.8 /-360.8 microg/dl, respectively; P<0.05). Administration of Gd-DTPA to iron-overloaded rats after renal pedicle ligation caused marked elevation of serum iron from baseline 143 /-3.4 to 570 /-8 microg/dl (P<0.0001). There were no changes of the named parameter, either in iron-overloaded anuric rats after saline injection or in normal diet uraemic animals, following Gd-DTPA administration. CONCLUSIONS: The combination of iron overload and lack of adequate clearance of Gd chelates may cause massive liberation of iron with dangerous elevation of free serum iron. It is highly recommended that after Gd contrast study, end-stage renal disease patients with probable iron overload should undergo prompt and intensive haemodialysis for prevention of this serious complication.- - - - - - - - - - ranking = 0.014104517904239keywords = contrast (Clic here for more details about this article) |
6/20. Photosensitive complex partial seizures aggravated by phenytoin.A 10-year-old girl is described with pure photosensitive complex partial seizures which consisted of a frightening visual phenomenon of seeing "shadow people," then staring blankly with lip smacking and sometimes becoming limp. The seizures were triggered by bright sunlight. With the institution of phenytoin therapy, her seizure frequency increased dramatically without any clinical evidence of toxicity and her phenytoin blood levels were within the therapeutic range. Discontinuation of phenytoin led to a return to baseline seizure frequency. The mechanism by which antiepileptic drugs may aggravate seizures is still not understood; therefore, awareness of this phenomenon is crucial for early diagnosis and appropriate treatment.- - - - - - - - - - ranking = 0.00072167296898079keywords = visual (Clic here for more details about this article) |
7/20. Usefulness of the nude mouse model in mesothelioma based on a direct patient-xenograft comparison.A patient with malignant mesothelioma experienced tumor recurrence 3 months after pleuropneumonectomy. Samples of the tumor were transplanted into nude mice to assess chemosensitivity. There was close concordance between the results in xenografts and the clinical outcome in this patient. Both mitomycin and to a lesser extent cisplatin were effective as single agents against the nude mouse xenografts, and the combination of these two drugs produced a complete response both in the patient and in the xenografts. The patient survived 18 months from onset of chemotherapy and 24 months from diagnosis. The duration of clinical complete response to chemotherapy was 14 months, despite the fact that mitomycin, the most effective agent against the xenografts, was discontinued after only two cycles because the patient developed pulmonary toxicity. This direct patient-xenograft correlation further validates the usefulness of the nude mouse model in the search for effective therapies for malignant mesothelioma, a tumor characterized by frequent refractoriness to most available agents.- - - - - - - - - - ranking = 0.2keywords = sensitivity (Clic here for more details about this article) |
8/20. cocaine-induced liver cell injury: comparison of morphological features in man and in experimental models.Although investigative research of animal models in cocaine metabolism and associated liver cell injury has been fairly extensive during the past 10 yr, little evidence of hepatotoxicity has been documented in man. We report a case of fulminant hepatic failure and acute rhabdomyolysis resulting from cocaine use. Coagulative-type perivenular and midzonal necrosis and periportal microvesicular fatty change were the predominant morphological features throughout all lobules of the liver, in contrast to periportal necrosis described in the only previous case report with biopsy. Differences in zonal necrosis caused by the same drug are not typically seen in man experiencing direct or indirect intrinsic hepatotoxicity. However, experimental models have shown cocaine to have this ability, dependent on enzyme induction or inhibition, sex and dose. Therapeutic approaches for prevention of possible liver cell injury by cocaine toxicity are discussed.- - - - - - - - - - ranking = 0.0070522589521193keywords = contrast (Clic here for more details about this article) |
9/20. Renal failure following radiologic procedures.Radiologic procedures that employ intravascular contrast material with or without angiography may lead to renal failure. In procedures that use intravenous contrast alone, the mechanism of renal injury is not precisely known, but direct toxicity to renal tubular cells is likely to be a major factor. Ionic and nonionic contrast agents are both capable of causing this adverse reaction. Renal failure occurring during angiography may also be secondary to the effects of radiocontrast, but the additional possibility that micro cholesterol emboli have been dislodged from atheroma located on the intima of large vessels must be considered. The acute or subacute development of renal failure in the presence of skin changes (livido reticularis), hypertension, multiple organ failure or dysfunction, and a fatal outcome favors the later diagnosis.- - - - - - - - - - ranking = 0.028209035808477keywords = contrast (Clic here for more details about this article) |
10/20. Fatal early onset group B streptococcal sepsis with normal leukocyte counts.In contrast to the attitude prevalent a decade ago, clinicians entertaining the diagnosis of neonatal bacterial sepsis now often place considerable reliance on the blood neutrophil count and degree of left shift. In this report we present four cases which illustrate that in some patients, no derangement of the complete blood count (CBC) is present early in the course of bacterial sepsis. In order to determine the length of time between bacterial inoculation and the appearance of changes in the CBC, we used an animal model of early onset Group B streptococcal sepsis. In adult animals we observed characteristic changes in the CBC within 1 hour of bacterial inoculation, but in neonates this latent period was considerably longer, lasting 4 hours. Thus a normal CBC might actually be expected during the first several hours of early onset neonatal sepsis. This delay in appearance of CBC changes constitutes a previously uninvestigated feature of neonatal neutrophil kinetics, the "latent period."- - - - - - - - - - ranking = 0.0070522589521193keywords = contrast (Clic here for more details about this article) |
| | Next -> |