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PubMed1994

Phase II trial of recombinant interleukin-1 beta in patients with metastatic renal cell carcinoma.

Interleukin-1 (IL-1) plays a central role in the immune system, partly by stimulating the production of interleukin-2 (IL-2) and other cytokines by lymphocytes. In preclinical studies, recombinant interleukin-1 (rIL-1 beta) has shown antitumor activity. We conducted a phase II trial to evaluate the efficacy of rIL-1 in metastatic renal cell carcinoma (RCC). rIL-1 beta was given at a dose of 50 ng/kg i.v. daily for 5 days on a 28-day schedule. Nineteen patients were registered; 16 completed two cycles and were evaluable for response. There were no complete or partial responses to treatment. Toxicity was generally mild and typically involved grades I and II fever, rigors, hypotension, and weight gain. Severe neurologic toxicity was seen in two patients, grade IV seizures were seen in one, and grade III somnolence was seen in another. Analysis of soluble IL-2 receptor (sIL-2r) levels revealed an increase from a mean pretreatment level of 4,567 pg/ml to a mean of 6,124 pg/ml posttreatment (p < 0.001). The mean pretreatment IL-6 level was 51 pg/ml, increased to 84 pg/ml posttreatment (p < 0.05). Patients with bulky disease had higher sIL-2r levels, and patients with tumor fevers had higher IL-6 and sIL-2r levels than patients without fever did. A neutrophilic leukocytosis and a mild thrombocytosis were observed in response to rIL-1 beta administration. We conclude that rIL-1 beta in this dose and schedule is inactive in metastatic RCC.

Adult↗
PubMedDate not supplied

Assessment of the toxicities of systemic low-dose interleukin-2 administered in conjunction with a melanoma peptide vaccine.

In this phase 2 study, the authors assessed the hematologic and clinical toxicities of a melanoma peptide vaccine administered in conjunction with low-dose interleukin-2 (IL-2) therapy. Forty patients were randomized to receive a weekly vaccine paired with a regimen of subcutaneous IL-2 (3 x 10(6) IU/m2/day) administered daily for 6 weeks beginning either at week 1 or at week 4 of vaccine therapy. The differences in the time course of the IL-2 between the two groups permitted assessment of the cause of the toxicities, due either to IL-2 or to vaccine components. Both treatment regimens were well tolerated in the outpatient setting. Toxicities attributable to the vaccine components were principally limited to grade 1 injection site reactions. Systemic clinical toxicities correlated with the initiation of IL-2 therapy. These toxicities coincided temporally and in magnitude with changes in circulating eosinophil counts, suggesting that systemic clinical toxicities and eosinophilia may have common etiologic pathways. Other minor toxicities attributable to this low-dose IL-2 regimen were clinically insignificant hepatic toxicity, mild anemia, and mild thrombocytosis. The hematologic effects of this therapy were delayed in time between the two treatment groups, without dramatic differences in magnitude, which suggests minimal modulation of the IL-2 toxicity by components of the vaccine.

Cancer Vaccines↗
PubMed2001

Ulcerative colitis and thrombotic thrombocytopenic purpura.

Inflammatory bowel disease is often associated with hematologic abnormalities such as anemia, leukocytosis, and thrombocytosis. We report for the first time an unusual case of ulcerative colitis complicated by thrombotic thrombocytopenic purpura. Severe lower gastrointestinal bleeding resolved with subtotal colectomy, but the thrombotic thrombocytopenic purpura proved unresponsive to medical treatment. Splenectomy and completion proctectomy were performed, ultimately resulting in a successful outcome.

Adult↗
PubMedDate not supplied

Once daily ceftriaxone for central nervous system infections and other serious pediatric infections.

Ceftriaxone has a very long serum half-life and enhanced in vitro activity against common pediatric pathogens. Therefore we evaluated the efficacy and safety of once daily ceftriaxone therapy in 57 children with serious infections including: meningitis (26 patients); ventriculitis (3); pyelonephritis (7); osteomyelitis (6); abscess (4); septic arthritis (3); sepsis (2); and miscellaneous infections (6). The most common isolates were Haemophilus influenzae (23), Escherichia coli (9) and Staphylococcus aureus (8). Ceftriaxone was given intravenously or intramuscularly in a dose of 50 mg/kg for non-central nervous system (CNS) infections. Patients with CNS infections received an initial dose of 100 mg/kg followed by 80 mg/kg 12 hours later and once daily thereafter. In a limited number of patients no major differences in serum ceftriaxone concentrations were found after intravenous or intramuscular injection. Of 57 patients with pathogens isolated 55 were completely cured; in one patient with Klebsiella pneumoniae ventriculitis, intraventricular gentamicin was briefly added to the regimen. Another patient with an anaerobic liver abscess recovered after metronidazole was administered. In three patients a delayed response to ceftriaxone was noted. One patient with previous recurrent infections had a second episode of H. influenzae meningitis 22 days after cessation of therapy. Clinical side effects were noted in 10 of 71 patients (including 14 treated patients who had negative cultures). Seven patients had diarrhea, one each had fever or rash and one had fever, rash and arthralgia. Laboratory side effects in 16 of 71 patients included eosinophilia (7), thrombocytosis (7), elevated liver enzymes (4) and leukopenia and neutropenia (2).(ABSTRACT TRUNCATED AT 250 WORDS)

Abscess↗
PubMed1993

Length of prediagnostic history related to the course and sequelae of childhood bacterial meningitis.

The relationship between length of prediagnostic history and course and sequelae of childhood bacterial meningitis was prospectively examined by collecting data from 286 children with bacteriologically confirmed bacterial meningitis. The cases were divided into three groups: short (< or = 24 hours, N = 141); intermediate (> 24 to 48 hours, N = 75); and long (> 48 hours, N = 70) history. The level of consciousness and serum C-reactive protein normalized sooner during hospitalization in patients with a longer history. They also showed neck stiffness more often and longer and had thrombocytosis earlier and more prominently than patients with a shorter history. The differences were not influenced by etiology, sex or age. The occurrence of neurologic abnormalities in the hospital or during the first 6 months after discharge was not affected by duration of illness before hospitalization. We conclude that our results support the view that bacterial meningitis presents in two forms. At presentation the more acute form often has a history of less than 24 hours and poses a great danger to the patient. In contrast the other form develops insidiously and is more difficult to detect but does not have a worse prognosis than the acute form.

Adolescent↗
PubMed1976

Multiple myeloma on polycythemia vera following radioactive phosphorus therapy.

A 74-year-old white man with established polycythemia vera was treated with radioactive phosphorus after phlebotomies alone failed to control his disease. About 2 3/4 years later he died of multiple myeloma. The mutagenic effect of radioactive phosphorus may have caused or possibly accelerated preexisting myeloma. Basic nonmalignant disease deserves careful consideration before radiation or radiomimetic agents are used. One might consider a probably less mutagenic drug such as hydroxyurea in patients with polycythemia vera when phlebotomy alone does not give good control of red cell mass and thrombocytosis.

Aged↗
PubMed1980

Smear platelet counts.

The average number of platelets per oil immersion field, in a count of ten oil fields, multiplied by 20,000 has proved to be a reliable estimation of platelets in normal and thrombocytopenic states. In the presence of thrombocytosis, ie, 25 or more platelets per oil immersion field, the smear count is less reliable. The multiplication factor of 20,000 was determined after statistical analysis of 288 consecutive unselected patients. Certain precautions should be observed, such as use of a fresh EDTA sample or freely flowing finger blood, a well made and well stained smear without platelet aggregates or precipitated stain particles, and an acceptable counting area on the film.

Blood Specimen Collection↗
PubMed1996

Chronic myeloid leukemia manifested during megakaryoblastic crisis.

We describe a 38-year-old man with a chronic myeloproliferative syndrome characterized by elevated white blood cell and platelet counts and increased blasts in the peripheral blood. Bone marrow aspiration was a "dry tap" and the biopsy specimen was hypercellular with numerous blasts, atypical megakaryocytes, and increased reticulin fibrosis. The blasts exhibited cytochemical reactivity for nonspecific esterase and PAS and immunohistochemically were positive for factor VIII, supporting megakaryoblastic lineage. Cytogenetic studies of peripheral blood revealed the t(9;22)(q34;q11). We interpreted these findings to be most consistent with chronic myeloid leukemia (CML) manifested at the time of megakaryoblastic crisis. Although the initial complete blood count showed leukocytosis and thrombocytosis, the patient subsequently had pancytopenia with clinical and pathologic findings consistent with acute myelofibrosis (AMF). Cytosine arabinoside and etoposide chemotherapy induced remission of the acute leukemia. We conclude that CML infrequently presents itself in megakaryoblastic crisis and that such cases may result in the clinicopathologic syndrome of AMF. The success of chemotherapy in this case also suggests that intensive antileukemic therapy may be useful in other patients with either CML-blast crisis or the clinicopathologic syndrome of AMF.

Adult↗
PubMed2001

Lipoprotein (a), thrombophilia and inflammatory bowel disease.

Thrombophilia in inflammatory bowel disease may be due to several risk factors, such as a dysbalanced haemostasis with a hypercoagulative state, thrombocytosis, hyperfibrinogenaemia and hyperhomocysteinaemia. In addition, increased concentrations of lipoprotein (a), a modified form of low-density lipoprotein particles, have been associated with a higher risk of thrombotic vascular disease, probably due to inhibition of (local and endothelial) fibrinolysis. The mechanisms regulating the plasma concentration of lipoprotein (a) have not yet been elucidated completely, but genetic factors are involved. Dietary factors seem to play a minor role. In this issue of the journal, Koutroubakis et al. report that lipoprotein (a) concentration is elevated in patients with Crohn's disease, but not in patients with ulcerative colitis. Several other (apo)lipoproteins have a different pattern in patients with inflammatory bowel disease than in a control population of healthy subjects from Crete. These findings add up to the multifactorial nature of thrombophilia in inflammatory bowel disease patients, especially in patients with Crohn's disease, and give rise to speculations about the clinical significance of the observed different lipoprotein metabolism in patients with inflammatory bowel disease.

Humans↗
PubMed2005

'Nipped in the Budd': hepatic venous outflow obstruction in evolution.

Hepatic venous thrombosis (Budd-Chiari) in evolution is a rare phenomenon and carries a high morbidity and mortality. We describe the case of a 39-year-old Bangladeshi lady who presented with severe abdominal pain secondary to a perforated duodenal ulcer and during her hospital admission developed an asymptomatic Budd-Chiari syndrome (BCS). Our report highlights the important role of an inflammatory focus, and how this process with an associated reactive thrombocytosis may act as a trigger for the development of BCS in an individual with predisposing risk factors. Our patient had been on the contraceptive pill, and was homozygous for the C677T mutation of 5,10-methylenetetrahydrofolate reductase, which results in hyperhomocysteinaemia. These pro-thrombotic risk factors were compounded by the thrombogenic potential of subsequent laparoscopic surgery, and resulted in an evolving thrombus that progressed into the inferior vena cava causing hepatic infarction. A particular feature of this case was the radiological demonstration of complete regression of the thrombus and the hepatic parenchymal changes, upon resolution of the inflammation and normalization of the platelet count. These changes occurred with oral anticoagulation as the only treatment modality, since our patient declined systemic thrombolysis. The demonstration of complete radiological resolution raises the question of how long one should continue oral anticoagulants and, indeed, whether in some instances a conservative approach may be the best management strategy for evolving BCS.

Adult↗
PubMed1992

New observations in a child with angiofollicular lymph node hyperplasia (Castleman's disease) originated from the mesenteric root.

Localized plasma cell type Castleman's disease (CD) is an unusual pathologic entity. It is frequently associated with clinical and laboratory characteristics and rarely occurs in children. Total surgical excision results in cure in all aspects. To make early diagnosis of mesenteric CD is not easy, especially for children. An 11-year-old Taiwanese boy was recently evaluated for anemia and delayed growth. His clinical findings included a syndrome of severe hypochromic microcytic anemia, neutropenia, thrombocytosis, hypoferremia, hypergammaglobulinemia, and growth failure. Radiological examinations (abdominal ultrasound, small intestinal series, and computerized tomography) identified hepatosplenomegaly, nephromegaly, and huge masses in the middle abdomen with precaval, celiac, and paraaortic lymph nodal enlargement. However, detailed physical examination failed to detect a mass. At laparotomy a double-fist-sized confluent mass was found arising from the mesenteric root. Most masses were discrete and were excised individually. The pathologic diagnosis was plasma-cell type angiofollicular lymph node hyperplasia (Castleman's disease). Seven weeks after surgery, he had an episode of acute hepatitis B. Postoperatively, he exhibited a dramatic growth spurt; the hemoglobin, red blood cell indices, serum iron, and immunoglobulins returned to normal in 2 months. Neutropenia, which has not been previously related to mesenteric CD, was an unexpected finding in our case; however, it resolved spontaneously 3 months after the surgery, suggesting its causal relationship with the tumor.

Castleman Disease↗
PubMed1994

Transient erythroblastopenia in a child with Kawasaki syndrome: a case report.

PURPOSE: We describe for the first time the case of a child with Kawasaki syndrome and associated transient erythroblastopenia. PATIENTS AND METHODS: A 5 1/2-month-old infant with Kawasaki syndrome as evidenced by lymphadenopathy, fever, rash conjunctival injection, and extremity changes had associated anemia and reticulocytopenia requiring transfusion and thrombocytopenia. Bone marrow aspiration was consistent with a transient erythroblastopenia. She developed cardiac aneurysms despite therapy with i.v. immunoglobulin and aspirin. RESULTS: The anemia and reticulocytopenia resolved with normalization of her hemoglobin. The platelet count increased and she developed a thrombocytosis characteristic of this clinical entity. She completely recovered without recurrence of either the anemia or reticulocytopenia. CONCLUSIONS: We speculate that the cause of the erythroblastopenia and thrombocytopenia is an inflammatory insult of Kawasaki syndrome on the bone marrow and its various lineages causing the myriad hematological abnormalities now associated with Kawasaki syndrome. It is possible that the i.v. immunoglobulin aids in neutralizing the triggering agent and therefore shortening the duration of the marrow insult.

Female↗
PubMed1996

Essential thrombocythemia in an infant.

PURPOSE: To report the unusual occurrence of essential thrombocythemia (ET) in a 5-month-old infant. PATIENTS AND METHODS: The child was referred by her pediatrician for a high platelet count detected on routine blood testing. The child was asymptomatic except for failure to thrive. Diagnostic tests to rule out secondary causes of thrombocytosis as well as myeloproliferative syndrome were done. RESULTS: The platelet count persisted at > 1,000,000/microliters, and no secondary cause could be established. The bone marrow aspirate and biopsy showed normal cellularity, no fibrosis, orderly maturation, and normal morphology of all three cell lines, with only an increase in the number of megakaryocytes. A diagnosis of ET was established as per the Polycythemia Vera Study Group criteria. In view of the young age of the patient and asymptomatic course of the disease, we decided to observe the child only, reserving antiplatelet agents for use in the event of a thromboembolic or hemorrhagic episode. CONCLUSIONS: This is the youngest known child with ET. We believe that conservative observation is warranted in an asymptomatic child. The child is currently doing well and is asymptomatic 4.5 years after diagnosis.

Female↗
PubMed2000

Diamond-Blackfan anemia.

Diamond Blackfan anemia is a rare congenital hypoplastic anemia that usually presents early in infancy. Congenital anomalies, in particular of the head and upper limbs, are present in about 25% of reported patients. The disease is characterized by a moderate to severe macrocytic anemia, occasional neutropenia or thrombocytosis, a normocellular bone marrow with erythroid hypoplasia, and an increased risk of developing leukemia. Recent genetic studies have led to the identification of mutations in the ribosomal protein RPS19 in approximately 25% of sporadic and familial cases, a second gene on chromosome 8p, and evidence for an additional locus (or loci). The pathogenesis is unknown. The majority of patients respond to prednisone, and often erythropoiesis can be maintained with low doses of the drug. Both remissions and increased resistance to steroid treatment can occur. Patients who do not respond to treatment are usually transfusion dependent, although responses to high dose steroid, androgen, and interleukin-3 have been observed. Bone marrow transplantation can be curative.

Combined Modality Therapy↗
PubMed2002

First histologic confirmation of the diagnosis made by the new wireless-capsule endoscopy.

Wireless-capsule endoscopy is a new painless technique for endoscopic imaging of the small bowel. A 63-year-old male with iron deficiency anemia and thrombocytosis and extensive negative workup was examined twice with the capsule and was found to have multiple bluish polypoid lesions with a villous-appearing texture. Some of these lesions actually were seen to be bleeding. This is the first time that we have obtained histologic evidence for lesions seen only on the video-capsule endoscopy. The lesion was reached by deep ileoscopy via colonoscopy. On histologic analysis, there was acute and chronic ileitis.

Capsules↗
PubMed2004

Correlation of platelet count with second-look laparotomy results and disease progression in patients with advanced epithelial ovarian cancer.

OBJECTIVE: To evaluate the significance of preoperative platelet counts in advanced epithelial ovarian cancer with respect to second-look laparotomy results and disease progression. METHODS: We prospectively evaluated 37 consecutive patients with advanced epithelial ovarian cancer who underwent primary surgical treatment. In addition to platelet counts, all patients were evaluated with respect to age, gravida, parity, and stage and grade of tumor. Thirty-six patients had stage III, and 1 patient had stage IV disease. Optimal debulking (diameter of residual tumor, less than 1 cm) was performed in all patients who subsequently received adjuvant chemotherapy (platin-paclitaxel). According to second-look laparotomy and follow-up results patients were divided into 2 groups. The first group had negative second-look laparotomy or no evidence of disease during follow-up (n = 20), and the second group had positive second-look laparotomy or progressive disease (n = 17). Sensitivity and specificity values were calculated for different cutoff values of platelet counts with receiver operating characteristic curve analysis. RESULTS: Age, gravida, and parity were not significantly different compared with controls (P >.05). Mean platelet counts were 371 x 109/L and 446 x 109/L in the first and second groups, respectively (P =.03). Different cutoff values of platelet counts for the diagnosis of thrombocytosis were evaluated. A cutoff value of 380 x 109/L had sensitivity 77% and specificity 60% for recurrence, whereas a cutoff value of 400 x 109/L had sensitivity 59% and specificity 65%. Area under the curve (+/- standard error) was 0.72 +/- 0.08 (P =.026). CONCLUSION: In patients with progressive disease and positive second-look laparotomy, preoperative platelet counts were significantly higher compared with patients with no evidence of disease on follow-up.

Carcinoma, Endometrioid↗
PubMed2005

Giant cell arteritis: laboratory tests at the time of diagnosis in a series of 240 patients.

The outcome of a patient with giant cell arteritis (GCA) is closely related to the development of severe ischemic manifestations. In the current study we analyzed the implications of routine laboratory tests obtained at the time of diagnosis in the clinical spectrum of a series of 240 consecutive patients with biopsy-proven GCA at the single hospital for a defined population. We also examined whether the laboratory markers of inflammation may be predictors of severe ischemic manifestations (visual ischemic events, cerebrovascular accidents, jaw claudication, or large-artery stenosis of the extremities of recent onset), and their potential correlation. Anemia (hemoglobin <12 g/dL) was observed in 131 (54.6%) and thrombocytosis in 117 (48.8%) patients. Sixty-eight (28.3%) patients had leukocytosis. The percentage of patients showing a significant increase of alkaline phosphatase and hypoalbuminemia was similar (25% and 27.8%, respectively). The mean values of erythrocyte sedimentation rate (ESR) and C-reactive protein were 93 +/- 23 mm/h and 94 +/- 63 mg/L, respectively. A strong correlation among most laboratory markers of inflammation was observed. Anemia was more commonly observed in patients without severe ischemic manifestations (61.5% versus 48.9% in those with severe ischemic manifestation; p = 0.05) and in patients with constitutional syndrome or fever (p < 0.001). Patients with ESR greater than 100 mm/h exhibited more commonly constitutional syndrome (p < 0.001) and had a statistically significant reduction in the incidence of visual ischemic events (p < 0.025). Only 7 (22.6%) of the 31 patients who suffered permanent visual loss had an ESR at the time of disease diagnosis greater than 100 mm/h. However, in a multivariate logistic regression analysis, only anemia was found to be a negative predictor for the development of severe ischemic manifestations of GCA (odds ratio, 0.53; 95% confidence intervals, 0.30-0.94; p = 0.03). In conclusion, our results suggest that some laboratory markers of inflammation, in particular the presence of anemia, may negatively predict the risk of severe ischemic complications in GCA patients.

Aged↗