Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adult wild-trapped opossums were infected with Leishmania donovani (Khartoum strain, WR 378) and evaluated as an animal model of visceral leishmaniasis. All infected opossums died within 32 days. Loss of body fat, hepatomegaly, and petechiae of skin and abdominal musculature were seen at necropsy. Microscopically, numerous amastigote-laden macrophages were seen in histologic sections of liver, spleen, and lymph nodes; fewer parasite-laden macrophages were in the bronchial-associated lymphoid tissues and renal glomeruli. Hematological findings included thrombocytopenia (terminal), neutropenia, and lymphopenia. Blood lymphocyte blastogenesis in response to concanavalin A and phytohemagglutinin was decreased markedly at day 24 post-infection (PI). Serum antibodies (1:40 dilution) to promastigotes of L. donovani were detected in five of eight infected opossums tested on days 10 and 24 PI. Total bilirubin concentrations and alanine aminotransferase and aspartate aminotransferase activities were increased after day 25 PI. Activated partial thromboplastin times and one-stage prothrombin times were prolonged before death. Concurrently, factors V, VIII, and XII activities were decreased.
 ...
PMID:Experimental visceral leishmaniasis in the opossum. 276 21

Disturbances of blood coagulation were studied in 32 consecutive patients with typhoid fever on their admission to hospital. Estimations of prothrombin time, activated partial thromboplastin time, fibrinogen, fibrin degradation products (FDPs), factors VII, VIII and XII, alpha I antitrypsin, plasminogen, CI esterase inhibitor, and platelet counts were performed as well as liver function tests and blood counts. Five patients had laboratory evidence of disseminated intravascular coagulation (DIC) and two had a generalised bleeding disorder which in the other three was inapparent. The platelet count in the group as a whole was low (P less than 0.05) and the FDPs in most cases were mildly elevated. The pre-kallikrein values were depressed in three of the five with DIC, whereas factor XII was not reduced. These results indicate that bleeding disorders in typhoid fever are uncommon. The depression of pre-kallikrein indicates that the DIC is probably triggered by activation of the intrinsic coagulation pathway. Most patients had lymphopenia and monocytopenia but only two had neutropenia.
 ...
PMID:Disturbances of blood coagulation associated with Salmonella typhi infections. 335 16

Six patients exhibiting severe pancytopenia or overt leukemia associated with myelofibrosis after chemotherapy for malignant disease have been investigated by immunologic techniques and ultrastructural cytochemistry. Initially, five patients displayed severe thrombocytopenia contrasting with mild neutropenia and anemia. Bone marrow biopsies showed a clear megakaryocytic proliferation and an excess of immature mononuclear cells. The demonstration of peroxidase activities at the ultrastructural level and immunofluorescence labeling with a panel of monoclonal antibodies, including an antiplatelet glycoprotein Ib and an antiglycoprotein IIb-IIIa complex, on blood or marrow cells, permitted identification of otherwise unidentifiable promegakaryoblastic proliferation. In two patients, the use of an immunoperoxidase technique with an antifactor VIII-R-Ag antibody has allowed direct confirmation of this diagnosis on bone marrow sections. This megakaryoblastic proliferation was not pure and was variably associated with blasts of other cell lines (erythroblasts or myeloblasts). Changes in the population of blasts were observed during evolution in two patients. The sixth patient had a mild thrombocytopenia associated with severe neutropenia and anemia. Bone marrow biopsy displayed a myelofibrosis and immature cells, without megakaryocytic proliferation. Ultrastructural study revealed a pure basophil-mast cell proliferation. In conclusion, in five of six patients with secondary acute leukemia associated with myelofibrosis, a proliferation of promegakaryoblasts was demonstrated using both immunofluorescent and ultrastructural cytochemical techniques.
 ...
PMID:Therapy-related leukemia associated with myelofibrosis. Blast cell characterization in six cases. 638 Jul 2

In an attempt to evaluate various clinical and laboratory features available within 24 h of admission, prior to the Widal test and bacteriological culture results as potential diagnostic aids in typhoid fever, we undertook a retrospective unit-based case control study in 90 febrile adult and paediatric patients admitted to King Edward VIII Hospital, Durban, South Africa with an initial diagnosis of typhoid fever. A total of 30 blood culture-proven typhoid fever patients (cases) were matched to 60 patients confirmed as not having typhoid fever (controls) by age, sex, race and severity of illness on admission. Features significantly associated with a final diagnosis of typhoid fever were: a pre-admission duration of fever > or = 7 days (odds ratio (OR) 6.9); hepatomegaly (OR 3.2); a normal leucocyte count (OR 10.8); a leucocyte count of < 10.0 x 10(3)/mm3 (OR 30.2); and leucopenia due to absolute neutropenia with a relative lymphocytosis (OR 11.8). Although the sensitivity, specificity and predictive values of any of these features cannot be used reliably to distinguish typhoid fever from other non-typhoidal febrile illness, it is concluded that leucopenia due to absolute neutropenia with relative lymphocytosis, when present, is highly suggestive of typhoid fever. A leucocyte count of > 10.0 x 10(3)/mm3 (OR 0.03) provides strong presumptive evidence against such a diagnosis.
 ...
PMID:The early diagnosis of typhoid fever prior to the Widal test and bacteriological culture results. 958 36

Infectious complications are an important cause of morbidity and mortality in cancer patients, especially those receiving chemotherapy. Furthermore, neutropenia, fever and infection limit the dose-intensity of antineoplastic chemotherapy in cancer patients. Fever without clinical signs of a localized infection is the commonest clinical presentation in neutropenic patients. Early empirical administration of broad-spectrum antibiotics at the onset of fever has become common practice, but the specific empirical regimen remains controversial. Guidance from therapeutic clinical trials is not straightforward, since it is difficult to compare trials, due to major differences and deficiencies in their design and analysis. Clinical trials fall into two categories: (i) explanatory trials which assess the hypothesis under ideal conditions, and (ii) pragmatic trials, which assess the regimen under the conditions of clinical practice. Methodological issues that are of crucial importance in the recognition of limits and value of the results of clinical trials in this field are discussed. The EORTC-IATCG has performed nine large therapeutic trials of empirical antibacterial and antifungal therapy in febrile, neutropenic patients with cancer. The results of trials, V, VIII, IX and XI are reviewed, and issues to be resolved in future trials are also considered.
 ...
PMID:The evolution of the empirical management of fever and neutropenia in cancer patients. 968 53

The combination of paclitaxel 135 mg/m2 (24-hour infusion) and cisplatin 75 mg/m2 is now considered the standard treatment in first-line chemotherapy for stage III suboptimally debulked and stage IV ovarian cancer. Interest is focused on the possibility of evaluating the combination of paclitaxel with carboplatin, because it was found to be less nefrotoxic and less neurotoxic than cisplatin. This study seeks to determine the maximum tolerated dose and to assess the antitumor activity of the combination of a 3-hour paclitaxel infusion followed by carboplatin. Thirty-three chemotherapy-naive patients with stage III-IV epithelial ovarian cancer entered this open, nonrandomized dose-finding study. The first dose level investigated was paclitaxel 125 mg/m2 and carboplatin 250 mg/m2: the dose level progression was performed by alternatively increasing paclitaxel 25 mg/m2 and carboplatin 50 mg/m2. Cycles were repeated every 28 days. At least three patients were treated at each dose level. Overall, 233 and 224 cycles, respectively, are evaluable for nonhematologic and hematologic toxicity. Dose-limiting toxicities (febrile neutropenia and severe fatigue) were observed in two of six patients at level VIII (paclitaxel 225 mg/m2 and carboplatin 400 mg/m2) and therefore the previous dose-level (paclitaxel 200 mg/m2 and carboplatin 400 mg/m2) was considered as the maximum tolerated dose. Neutropenia (grade 3-4 in 63% of cycles), neurotoxicity (grade 2 in 37.5% and grade 3 in 9% of patients), arthromyalgias (grade 2 in 53% of patients and grade 3 in 3% of patients), and grade 3 alopecia were the most common toxicities observed. The incidence of thrombocytopenia was low (grade 3 in 4% of cycles) and no renal toxicity was observed. An objective remission was documented in 74% of 31 evaluated patients, including eight complete remissions (26%) confirmed by second-look surgery. The combination of paclitaxel 200 mg/m2 3-hour infusion followed by carboplatin 400 mg/m2 (30-minute infusion) is a safe and active regimen as first-line chemotherapy for advanced ovarian cancer.
 ...
PMID:The combination of paclitaxel and carboplatin as first-line chemotherapy in patients with stage III and stage IV ovarian cancer: a phase I-II study. 978 7

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death in the world. Traditional chemotherapy for advanced NSCLC is often considered excessively toxic. Recent clinical trials documented that gemcitabine may represent a good therapeutical option in patients with NSCLC. Aim of our research was to retrospectively evaluate the adverse effects induced by gemcitabine in patients with NSCLC from 1 January 1997 to 31 December 2002, in clinical records of Oncology Divisions of "S. Giovanni di Dio" Hospital of Crotone, "Ospedali Riuniti" Hospital of Reggio Calabria, Hospital of Paola, and in Pneumological Oncology Division of "Mariano Santo" Hospital of Cosenza, Italy. Clinical records of patients treated with gemcitabine (1000mgm(-2) on days 1 and 8) were reviewed and following data were obtained: sex and age of the patients, histologic diagnosis and disease stage, World Health Organisation (WHO) performance status and toxic effects induced by gemcitabine. We reported that 71.6% of NSCLC patients (age range 48-77 years; 135 males, 27 females; performance status 0=53, 1=109) were eligible for our study. Side effect of gemcitabine involved gastrointestinal system (nausea, vomiting and diarrhoea) and only in the last cycles (VIII-XI) emopoiethic system (leukopenia, neutropenia, thrombocytopenia and anemia). Grade IV vomiting occurred in three patients, thrombocytopenia in two. Grade III leukopenia was observed in three patients. Other toxicities were mild. None of the patients died during chemotherapy. In conclusion, these data showed that gemcitabine present a very good tolerability in patients with NSCLC. Therefore, it could be considered as a new therapeutic agents to use as first line therapy for this disease.
 ...
PMID:Retrospective analysis of adverse drug reactions induced by gemcitabine treatment in patients with non-small cell lung cancer. 1472 22

Neonatal encephalopathy manifests with altered sensorium, tone abnormalities, and often with abnormal movements and seizures. The causes are heterogeneous and many. We report a late preterm neonate who presented with depressed sensorium, cranial nerve abnormalities, mixed hypertonia and hypotonia, and respiratory failure. Neuroimaging and electrophysiological studies were normal. She had neutropenia and elevated lactates in blood. Her dried blood spot analysis by tandem MS/MS showed normal acylcarnitine and amino acid profile. Plasma and cerebro spinal fluid (CSF) amino acid quantification were inconclusive, CSF folate was normal. Urine organic acid analysis showed elevated lactate. Semi-quantitative analysis of urine showed borderline elevation of 3-methylglutaconic acid. Diagnosis of 3-methylglutaconic aciduria (3MGA) type VIII was suggested by whole-exome sequencing, which revealed a homozygous, likely pathogenic, missense mutation in Exon 2 of HTRA2 gene (chr2.74757898A>C). Her parents were found to be carriers of the same mutation. This underscores the importance of genetic studies in the evaluation of neonatal neuro-metabolic disorders. We report the first case of 3MGA type VIII from our region with a review of already reported 11 cases.
 ...
PMID:3-Methylglutaconic aciduria type VIII in an Indian neonate. 3244 93