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PubMed1976

Coagulation factor XIII concentration in sickle-cell disease.

Plasma factor XIII was assayed serially for a 1 1/2 to 2 year period in four patients with sickle-cell disease (SSD), during which several episodes of SSD crisis were observed. During crisis-free periods, plasma factor XIII concentration was lower than in normal subjects. With crisis onset, there was usually a concomitant fall in platelets and in plasma factor XIII soon after followed by a rise in fibrinogen concentration and platelet count. Following crisis resolution there was an increase in plasma factor XIII concentration peaking 3 weeks after crisis onset and occurring at the time of subsidence of thrombocytosis. It is suggested that the observed changes in plasma factor XIII concentration in SSD patients support the hypothesis that in the early stage of SSD crisis, fibrin deposition and/or thrombosis significantly enhance the role of sickled erythrocytes in producing vascular occlusion and/or organ infarction.

Adult↗
PubMed1998

[Pheochromocytoma manifesting as toe necrosis].

BACKGROUND: Cutaneous manifestations of pheochromocytoma other than sweating, and facial pallor during paroxysmal episodes of hypertension are exceptional. CASE REPORT: We observed partial necrosis of the fourth toes which revealed pheochromocytoma. DISCUSSIONS: Signs of peripheral vascular disease are uncommon during the course of pheochromocytoma. Only four cases have been reported in the literature. Occurrence of distal necrosis in combination with hypertension and palpable pulses is suggestive of pheochromocytoma requiring assay of urinary catecholamines. The pathogenic mechanisms of necrosis would be vasospasm of cutaneous vessels due to excessive plasmatic catecholamine levels and thrombocytosis as an aggravating factor.

Adrenal Gland Neoplasms↗
PubMed1981

Hyporeninemic hypoaldosteronism. An overlooked cause of hyperkalemia.

To establish the frequency and clinical and biochemical characteristics of hyporeninemic hypoaldosteronism (HH), we reviewed 100 consecutive cases of hyperkalemia (potassium content > 5.3 mEq/L). The most common cause was end-stage renal failure (34%). Other causes included overzealous potassium replacement, spironolactone therapy, hemolysis, acute renal failure, acidosis, thrombocytosis, and Addison's disease. Ten of 19 patients with unexplained hyperkalemia showed suppressed renin (0.12 to 1.3 ng/mL/hr) and aldosterone (5.4 to 21.6 ng/dL) responses to furosemide-posture challenge. Cortisol reserve was normal in HH. Fludrocortisone acetate therapy corrected the hyperkalemia. Other features of HH include low serum bicarbonate content, mild renal insufficiency, diabetes, and advanced age. The use of indomethacin and ibuprofen was associated with one case of HH each. Results suggest that HH is an overlooked cause of hyperkalemia, especially in patients whose hyperkalemia is unexplained.

Adult↗
PubMed2003

An improved definition of immune heparin-induced thrombocytopenia in postoperative orthopedic patients.

BACKGROUND: Diagnosis of immune heparin-induced thrombocytopenia (HIT) is usually based on a fall in platelet count below 150 x 109/L (standard definition of thrombocytopenia). However, this definition may be inappropriate for postoperative patients who often develop postoperative thrombocytosis. We sought to determine an improved definition of thrombocytopenia indicating HIT in postoperative orthopedic patients, including its impact on frequency and thrombotic risk of HIT. METHODS: We performed a secondary analysis of a clinical trial of 665 patients who received unfractionated or low-molecular-weight heparin following elective hip arthroplasty. Daily platelet counts and objective studies for deep vein thrombosis were performed in all patients. Laboratory detection of HIT antibodies from a 362-patient subgroup was used to define sensitivity and specificity of various definitions of thrombocytopenia to indicate HIT. RESULTS: The improved definition of HIT was a 50% or greater platelet count fall from the postoperative peak, as this definition had greater sensitivity (50% vs 25%) and similar high specificity (99.1% vs 99.4%) for detecting HIT-IgG compared with the standard definition. Patients with HIT who were identified using the improved definition had a higher frequency of thrombosis than patients without HIT (72.2% vs 17.3%; P<.001). The improved definition showed an even greater absolute difference in frequency of HIT between unfractionated and low-molecular-weight heparin (4.8% vs 0.6%; P<.001) compared with the standard definition (2.7% vs 0%; P =.002). CONCLUSION: A 50% or greater fall in the platelet count from the postoperative peak is a sensitive definition indicating possible HIT that is associated with an increased risk of thrombosis.

Anticoagulants↗
PubMed1993

Identifying high-risk patients before head and neck oncologic surgery.

Patients from the Comprehensive Cancer Center of the Arthur G. James Cancer Hospital and Research Institute, Ohio State University, Columbus, who were undergoing major head and neck oncologic surgery were prospectively studied to determine predictors of postoperative medical complications and wound infection. Of 119 patients studied, 28 (24%) had at least one postoperative medical complication. The strongest predictors of medical complication were poor functional capacity as assessed by the Specific Activity Scale questionnaire and alcohol abuse. Thirteen patients (11%) developed wound infections. The strongest predictors of wound infection were an elevated preoperative platelet count and prolonged surgery. Wound infection was the strongest correlate of prolonged hospital stay. These findings suggest that the Specific Activity Scale questionnaire identifies patients at risk for medical complication, that alcohol abuse should be managed aggressively, and that thrombocytosis identifies patients at risk for wound infection.

Adult↗
PubMed1982

Moxalactam in the treatment of pediatric infections.

The clinical efficacy and safety of the new oxacephalosporin moxalactam disodium were evaluated in 54 children with a variety of pediatric infections. Except for a terminally ill neutropenic leukemic patient with pneumonia and sepsis due to Pseudomonas aeruginosa who died shortly after initiation of therapy, moxalactam treatment was effective in all patients. No recurrent infections were observed. The rate of clinical response to moxalactam appeared to be at least comparable to that of patients treated with traditional antibiotics. In vitro sensitivity testing demonstrated that all bacteria isolated except P aeruginosa were sensitive to moxalactam while Haemophilus influenzae was exquisitely sensitive. Side effects included thrombocytosis (five patients), transient SGPT elevations and eosinophilia (three each), fever with rash (one), and neutropenia (one). In one patient, superinfection with Streptococcus faecalis developed. We conclude that moxalactam may be a useful antibiotic in pediatrics, particularly for the treatment of infections due to H. influenzae and Enterobacteriaceae. Its role in infections caused by group B streptococcus and Pseudomonas awaits further studies.

Adolescent↗
PubMed1983

Ceftriaxone therapy in pediatric patients.

Twenty-six children, aged 2 months to 15 years, were treated with intravenous ceftriaxone sodium, 37.5 mg/kg every 12 hours, for an average of seven days. Clinical and microbiologic cures occurred in 19 of 21 patients, from whom bacterial pathogens were cultured. Ceftriaxone was not effective in treating an 18-month-old infant with periorbital cellulitis caused by relatively resistant Staphylococcus aureus. A relapse occurred in a 2-month-old infant with meningitis caused by ceftriaxone-sensitive Salmonella. Eleven patients had transient diarrhea, superficial candidiasis developed in ten patients, and one patient experienced skin flushing during administration of the antibiotic. Transient asymptomatic laboratory abnormalities were detected in 15 patients; nine patients had elevated serum concentrations of transaminases or bilirubin, 11 had thrombocytosis, three experienced eosinophilia, and one had thrombocytopenia. Transient suppression of normal flora of the intestine occurred in 21 patients. Side effects were not serious enough to warrant discontinuing ceftriaxone therapy in any patient.

Adolescent↗
PubMed1986

Aztreonam therapy for serious gram-negative infections in children.

Fifty-nine children were enrolled in an open trial of aztreonam, a monocyclic beta-lactam, therapy for serious gram-negative infections. Thirty-six infections were microbiologically evaluable and received five or more days of therapy. Patients' ages ranged from 3 days to 12 years, and diagnoses included pyelonephritis or cystitis (20), deep soft tissue or joint infection (seven), septicemia (four), pneumonia (three), peritonitis, and epiglottitis. Causative bacteria included Escherichia coli and other Enterobacteriaceae, Pseudomonas aeruginosa, and Haemophilus influenzae. The standard regimen was 30 mg/kg every six or eight hours intravenously. All isolates were aztreonam-susceptible and were eradicated during therapy. Two patients had microbiologic relapses: a patient with Salmonella choleraesuis meningitis who was initially treated for only ten days and a patient with E coli pyelonephritis. Clinical cure was achieved in 31 of 36 children. Pharmacokinetic studies performed in six children demonstrated no difference in serum concentrations or pharmacokinetic variables between day 1 and day 7 of therapy. Although several patients had transient eosinophilia (eight), elevated levels of aminotransferase (seven), or thrombocytosis (ten), no clinically significant adverse effects were noted. In this initial, uncontrolled study, aztreonam was effective and safe in the treatment of a variety of serious gram-negative infections in children.

Aztreonam↗
PubMed1993

Splenic abscess in the intensive care unit.

BACKGROUND AND METHODS: From 1980 through 1990, nine patients developed de novo splenic abscess during their stay in our intensive care unit (ICU), representing the first series of such reported cases. RESULTS: All nine patients were septic prior to the diagnosis of splenic abscess. The signs and symptoms of splenic abscess commonly described in the literature were of little help in detecting this pathology in ICU patients. Mean +/- SD platelet count, however, increased significantly, from 274 x 10(9)/L +/- 50 x 10(9)/L at admission to 647 x 10(9)/L +/- 94 x 10(9)/L at diagnosis. At diagnosis, left pleural effusion was present in all patients. Only three patients had detectable left upper quadrant tenderness. Abdominal computed tomographic scans, when used, were diagnostic in all cases. All patients were treated by splenectomy; eight had a solitary abscess. Six abscesses were caused by enteric organisms, two by Staphylococcus aureus, and one by Streptococcus epidermidis. Eight patients (89%) had had the offending organism previously isolated from their blood or from another infected site. Mortality was 45%. CONCLUSIONS: Splenic abscess, although a rare clinical entity, does occur de novo in ICU patients and is associated with significant mortality. Unexplained thrombocytosis in a septic ICU patient with persistent left pleural effusion is suggestive of splenic abscess. Previous culture and sensitivity results are useful in guiding perioperative antibiotic choices.

Abscess↗
PubMed1996

Leukemogenic risk of hydroxyurea therapy in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis.

In polycythemia vera (PV), treatment with chlorambucil and radioactive phosphorus (p32) increases the risk of leukemic transformation from 1% to 13-14%. This risk has been estimated to be 1-5.9% with hydroxyurea (HU) therapy. When compared with historical controls, the risk with use of HU does not appear to be statistically significant. The leukemogenic risk of HU therapy in essential thrombocytosis (ET) and in myelofibrosis with myeloid metaplasia (MMM) is unknown. HU remains the main myelotoxic agent in the treatment of PV, ET, and MMM. We studied 64 patients with these three disorders, seen at our institution during 1993-1995. The patients were studied for their clinical characteristics at diagnosis, therapies received, and development of myelodysplasia or acute leukemia (MDS/AL). Forty-two had PV, 15 ET, and 6 MMM, and 1 had an unclassified myeloproliferative disorder. Of the 42 patients with PV, 18 were treated with phlebotomy alone, 16 with HU alone, 2 with p32, 2 with multiple myelotoxic agents, and 2 with interferon-alpha (IFN-alpha). Two patients from the phlebotomy-treated group, one from the HU-treated group, and 1 from the multiple myelotoxic agent-treated group developed MDS/AL. In the larger group, 11 received no treatment or aspirin alone, 18 were treated with phlebotomy alone, 25 with HU, 5 with multiple myelotoxic agents, 2 with p32, 2 with IFN-alpha, and 1 with melphalan. Study of the entire group of 64 patients showed that only one additional patient (total of 5 out of 64) developed MDS/AL. This patient had been treated with HU alone. Statistical analysis did not show any association between clinical characteristics at diagnosis, or HU therapy, and development of MDS/AL (P=0.5). Thus, our data provide no evidence suggestive of increased risk of transformation to MDS/AL with HU therapy in PV, ET, and MMM. Larger, prospective studies are needed to study this issue further.

Acute Disease↗
PubMed1999

Erythropoietin receptor and hematological disease.

This review will discuss evidence for the role of the erythropoietin (Epo) receptor in the development of erythrocytosis and other hematological disorders. The possible causative role of mutations of other genes in the pathogenesis of idiopathic erythrocytosis will be considered. Polycythemia vera (PV) is a myeloproliferative disorder that is caused by an undefined stem cell abnormality, characterized by a significant erythrocytosis, leukocytosis, and thrombocytosis. However, erythrocytosis may arise from apparent (or relative) polycythemia in which the hematocrit is raised due to a low plasma volume. In such cases the red cell mass is normal. A group of disorders with increased red cell mass caused by stimulation of erythrocyte production is known as secondary polycythemia. Investigation of such patients may reveal a congenital abnormality such as high affinity hemoglobin or an acquired abnormality caused, for example, by smoking, renal vascular impairment, or an Epo-producing tumor. Even after thorough examination there remains a cohort of patients for whom no definite cause for the erythrocytosis can be established. A careful clinical history may reveal whether this idiopathic erythrocytosis is likely to be congenital and/or familial, in which case the term "primary familial and congenital polycythemia" is sometimes applied. Access to a range of laboratory investigations may define the molecular pathophysiology. We will now discuss how this process can be investigated.

Hematologic Diseases↗
PubMed1997

Granulocyte colony-stimulating factor and interleukin-6-producing lung cancer cell line, LCAM.

BACKGROUND AND OBJECTIVES: We describe a case of granulocyte colony-stimulating factor (GCSF) and interleukin-6 (IL-6)-producing lung cancer. METHODS: A 53-year-old man underwent left upper lobectomy under diagnosis of lung cancer. The tumor obtained by a preoperative biopsy was analyzed. RESULTS: Preoperative data showed leukocytosis with left-shift of leukocytic morphology and thrombocytosis and an elevated serum GCSF level. Histological examination revealed poorly differentiated adenocarcinoma. A cell line, named LCAM, was established from the tumor and the cytokines in the culture medium were measured by enzyme immunoassay. GCSF and IL-6 were produced in large amounts by LCAM, but granulocyte-macrophage colony-stimulating factor (GMCSF) and interleukin-3 (IL-3) were not. A proportion of LCAM expressed GCSF receptor on the cell surface, but IL-6 receptor could not be detected. LCAM proliferation was inhibited in the culture with antihuman GCSF antibody in a dose-dependent manner. CONCLUSIONS: We suggest that LCAM proliferation is positively regulated by GCSF.

Granulocyte Colony-Stimulating Factor↗
PubMed1999

Clinical picture, response to therapy, and survival of women with diffuse malignant peritoneal mesothelioma.

BACKGROUND AND OBJECTIVE: The clinical picture, response to therapy, and prognosis of women with diffuse malignant peritoneal mesotheliomas (DMPM) are ill defined. The purpose of this study is to report on the clinical picture, response to therapy, and survival of women with DMPM. METHODS: The study is a retrospective review of 15 women with the confirmed pathologic diagnosis of DMPM treated between 1964 and 1996. Survival curves were constructed according to the Kaplan-Meier method. The effect of different factors on survival was studied using the log-rank test. Two-tailed P values < 0.05 were considered significant. RESULTS: Clinical features included abdominal distension (11/15, 73%), abdominal pain (6/15, 40%), ascites (9/15, 60%), abdominal or pelvic masses (14/15, 93%), elevated CA-125 (4/4, 100%), thrombocytosis (4/ 15, 27%), and thrombo-embolic manifestations (3/15, 20%). The response rate to all first-line chemotherapy regimens was 30%. The response rate to paclitaxel/cisplatin was 66.7% and the toxicity was tolerable. The median survival of all patients was 12.5 months. Patients who underwent cytoreductive surgery survived longer than those who underwent biopsy only (median survival 13.5 vs. 6.0 months, P = 0.24). Patients who received chemotherapy survived significantly longer than those who did not receive chemotherapy (29.0 vs. 1.0 months, P = 0.03). Patients who responded to first-line chemotherapy survived significantly longer than those who did not respond (P = 0.04). CONCLUSIONS: Cytoreductive surgery and chemotherapy, especially with paclitaxel and cisplatin, might be of benefit in women with DMPM.

Abdominal Pain↗
PubMed1997

Role of interleukin-6 in the paraneoplastic inflammatory syndrome associated with renal-cell carcinoma.

We investigated the possible causative role of interleukin 6 (IL-6) in the paraneoplastic inflammatory syndrome and in paraneoplastic cholestasis (Stauffer syndrome) associated with renal-cell carcinoma in a series of 119 patients with metastases. IL-6 levels were found significantly higher in patients with paraneoplastic fever and weight loss. Patients with detectable serum IL-6 (n = 90, 76%) had significantly higher serum CRP, haptoglobin, and serum alkaline-phosphatase and gammaglutamyl-transferase levels. Platelets, polymorphonuclear neutrophil (PMN) and monocyte counts were also significantly higher in patients with detectable serum IL-6; in contrast, hemoglobin levels were significantly lower in patients with serum IL-6 over 80 pg/ml. Three of these patients were included in a phase-II trial of an anti-IL-6 monoclonal antibody given daily during 21 days. Reductions of CRP, haptoglobin and serum alkalin phosphatases were observed in all 3 patients during anti-IL-6 administration, with a subsequent increase up to or above pre-treatment levels after the end of anti-IL-6. Decrease of platelets, PMN and monocyte counts were also observed in the 3 patients during anti-IL-6 administration, with a normalization of cell counts in a patient with increased platelets, PMN and monocyte counts. Hemoglobin concentration, serum albumin concentration and lymphocyte counts remained stable in the 3 patients during and after anti-IL-6 administration. Serum IL-6, as evaluated by IRMA, decreased in the 3 patients during anti-IL-6 administration, but increased above pre-treatment levels after the end of anti-IL-6 administration. These results demonstrate that IL-6 is involved in the physiopathology of paraneoplastic syndromes observed in patients with metastatic renal-cell carcinoma, in particular CRP and haptoglobin increase, paraneoplastic cholestasis, also paraneoplastic thrombocytosis, neutrophilia and monocytosis.

Alkaline Phosphatase↗
PubMed1977

Hepatoblastoma in infant sister and brother.

Two infants, a sister with motor retardation and brother with slight microcephaly and an undescended testis, died of hepatoblastoma. Only another documented familial occurrence of this tumor, affecting siblings of the same sex, can be found in the literature. The two patients described in this paper exhibited high platelet counts prior to liver resection. Although iron deficiency may have contributed to the thrombocytosis, the finding of many megakariocytes within the hepatoblastomas suggests an intra-tumoral production of platelets. An epidemiological investigation of the family under study failed to yield conclusive data. Hepatoblastoma is a rare tumor, but it may affect more than one sibling. Therefore, periodic clinical and laboratory evaluations of the siblings at risk appear to be justified.

Carcinoma, Hepatocellular↗
PubMed1979

Idiopathic refractory sideroblastic anemia: incidence and risk factors for leukemic transformation.

The clinical course of 29 patients with idiopathic refractory sideroblastic anemia studied by us was reviewed. Four patients developed acute leukemia. We were able to find 27 out of 268 cases of idiopathic refractory sideroblastic anemia reported in the literature which terminated in acute leukemia. Nine of these were well described. The overall incidence of acute leukemia is 10%. In an attempt to identify the risk factors for the development of acute leukemia, the clinical and laboratory features of this group of thirteen well-described cases which terminated in acute leukemia were compared to the remaining 25 of our cases which did not undergo leukemic transformation. The patients who died of acute leukemia tended to have a more severe anemia, a lower reticulocyte count, and increased transfusion requirement, and thrombocytopenia. Thrombocytosis appears to be a relatively good prognostic sign.

Adult↗
PubMed1980

Myeloproliferative syndrome with sideroblastic anemia and acquired hemoglobin H disease.

Hemoglobin H disease usually occurs as a result of inheritance of the genes for alpha thalassemia; however, occasionally patients acquire hemoglobin H in association with hematologic malignancy. This report concerns a 63-year-old Filipino man with a myeloproliferative syndrome with marked thrombocytosis and apparently acquired hemoglobulin H disease. The patient had hemolytic anemia, dimorphic red blood cells (RBC) and abundant ringed sideroblasts in the marrow. The peripheral blood contained 27% hemoglobin H and about two-thirds of his RBC had hemoglobin H inclusion bodies. There was no previous history of anemia or evidence of thalassemia in two siblings or nine adult children of the patient. In vitro studies of globin chain synthesis documented markedly decreased production of alpha globin with alpha/beta biosynthetic ratios of 0.05 in peripheral blood reticulocytes and 0.10 in bone marrow cells. The relative concentration of mRNA for alpha globin was approximately 20-fold less than that of beta globin, apparently accounting for the deficiency in alpha globin synthesis.

Anemia, Sideroblastic↗
PubMed1984

Disseminated aspergillosis presenting with endophthalmitis. A case report and a review of the literature.

A patient with idiopathic thrombocytosis developed sudden loss of vision in his left eye secondary to endophthalmitis caused by Aspergillus flavus. He subsequently manifested other symptoms and signs of disseminated infection, and eventually died despite prompt initiation of appropriate parenteral antifungal therapy. A period of profound, iatrogenic neutropenia preceded the development of his terminal infection. Previously reported cases of hematogenously acquired Aspergillus endophthalmitis are reviewed, and approaches to diagnosis and management are discussed. The frequency of eye involvement in cases of disseminated aspergillosis is unknown, but it may be greater than appreciated previously.

Adolescent↗