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PubMed1977

Angioimmunoblastic lymphadenopathy: common symptoms, uncommon diagnosis.

After five months of treatment for what was believed to be tuberculosis, a 49-year-old woman had recurrence of high spiking fever, lymphadenopathy, and malaise along with an intermittent maculopapular rash. Other findings were a positive Coombs test, iron deficiency, elevated gamma globulin levels, polyclonal gammopathy, and hepatosplenomegaly. Biopsy of a cervical lymph node revealed an angioblastic pattern consistent with angioimmunoblastic lymphadenopathy. Review of biopsy material obtained six months previously showed the same changes. Antituberculosis therapy was discontinued, and a regimen of prednisone and iron replacement was begun. The patient did well initially; when symptoms returned, they were controlled by adding azathioprine to the regimen for steroid-sparing effect. However, serologic abnormalities returned and within a few months, symptoms exacerbated; despite intensive medical therapy, the patient died. Angioimmunoblastic lymphadenopathy is a recently recognized disorder with a usually progressive course. No treatment has yet been established as effective, and death usually occurs within one year after diagnosis.

Diagnosis, Differential↗
PubMed1987

Differentiation of Brucella abortus and Yersinia enterocolitica serotype 09 infections in cattle: the use of specific lymphocyte transformation and brucellin skin tests.

The lymphocyte transformation test (using an in vitro whole-blood lymphocyte stimulation procedure) and the Brucellin skin test were applied to five heifers infected with virulent Brucella abortus strain 544, five cows inoculated with Yersinia enterocolitica serotype 09, and four non-exposed cows. Lymphocytes from Brucella-inoculated animals persistently gave very high blastogenic reactions indicative of active Brucella infection. The test was persistently negative in Yersinia-infected and non-exposed cattle. Four of the five cows infected with Yersinia enterocolitica type 09 and all four control cattle were persistently negative to the delayed hypersensitivity skin reaction with brucellin. All cattle infected with Yersinia enterocolitica type 09 were strongly positive to the Rose Bengal, Serum agglutination, Complement fixation and Antibovine globulin tests using Brucella abortus antigens. One lactating cow infected with Yersinia enterocolitica type 09 was positive to Brucella milk ring test. These results indicate that standard Brucella serological tests are unreliable in differentiating the two infections in cattle and that both the Lymphocyte transformation and brucellin skin tests could be used to differentiate bovine brucellosis from yersiniosis.

Agglutination Tests↗
PubMedDate not supplied

Autoimmune hemolytic anemia preceding T-ALL in a five-year-old girl.

A 5-year-old girl developed acute lymphoblastic leukemia (T-ALL) 15 months after being diagnosed with autoimmune hemolytic anemia (AHA), while AHA was in partial remission. AHA was mediated by warm antibodies. Because AHA could not be controlled during the induction therapy of ALL, she was administered immunoglobulin G and plasmapheresis was performed. Hepatomegaly dissappeared in the 4th month. However, anemia requiring blood transfusion, positive direct Coombs' test, and splenomegaly dissappeared in the 13th month of the leukemia treatment; reticulocytosis and decreased haptoglobin level persisted. AHA exacerbated in the 24th month of the ALL therapy. Prednisolone was started but the family refused to continue the therapy. This case presents some features that were not reported before, such that ALL was preceded by AHA and involved T-cell lineage, AHA was mediated by warm antibodies, and the two disorders took place in childhood.

Anemia, Hemolytic, Autoimmune↗
PubMed2003

Immunosuppressive treatments for myelodysplastic syndromes.

The myelodysplastic syndromes (MDS) comprise a heterogeneous group of clonal hematopoietic stem cell disorders, while, immunological abnormalities are frequently observed in patients with MDS. Several reports revealed that about 10% of MDS patients have clinical autoimmune disorders like skin vasculitis, rheumatic disease, or autoimmune hemolytic anemia. Furthermore, serological immunological abnormalities like hyper- or hypogammaglobulinemia, positivities of antinuclear antibody, positivities of direct Coombs test, or inverted CD4/8 ratios were found in 18-65% of patients with MDS. Recently immunosuppressive therapies including prednisolone, antithymocyte globulin, and cyclosporin A (CsA) are used to treat cytopenia in some patients with MDS. We examined the efficacy of CsA in 50 patients with MDS. Hematologic improvement was observed in 30 (60%) patients especially for erythroid lineage. There were significantly more responders with good karyotype or DRB1*1501 than with intermediate/poor karyotypes or with other HLA types. MDS with erythroid hypoplasia is a rare form of MDS, and has not yet been clearly defined. We reported four patients with MDS with erythroid hypoplasia who had morphological evidence of myelodysplasia and low percentage of erythroid precursors. Rearrangements of the TCR-beta and -gamma genes were seen in these patients using Southern blot and PCR analysis. Also they had skewed TCR usages using TCR repertoire analysis. Their anemia drastically improved with CsA therapy. We have to establish the clinical usefulness of immunosuppressive therapy in MDS patients and simple tools for revealing T-cell mediated myelosuppression in the individual patients for decision-making.

Autoimmune Diseases↗
PubMed1967

Immunopathology of NZB/BL mice. VI. Virus separable from spleen and pathogenic for Swiss mice.

Hemolytic disease characterized by slight anemia, reticulocytosis, hemosiderosis, extramedullary hematopoiesis, and positive indirect antiglobulin (Coombs') tests and renal disease with proteinuria, hypoalbuminemia, and glomerular lesions were produced in Swiss mice by neonatal intraperitoneal inoculation of cell-free filtrates prepared from the spleens of old NZB/Bl mice. Lymphoid cell and plasma cell hyperplasia as well as hypergammaglobulinemia occurred in some of these inoculated mice. Type "C" murine oncogenic virus-like particles, indistinguishable from those previously described (1), were shown by electron microscopic study to be present in distinctive locations, notably in the basal foldings of convoluted tubules in the kidneys of a newborn NZB/Bl mouse, old NZB/Bl mice, a CBA x NZB F(1) hybrid mouse, and a Swiss mouse inoculated with NZB/Bl spleen cell-free filtrate. These observations point to two (perhaps related) circumstances which may be requisites for the pathogenic action of this newly discovered virus within and outside the strain NZB: infection of newborn, or infant, mice; persistent, possibly tolerant, infection of adult mice.

Anemia, Hemolytic↗
PubMed2005

Hemolytic anemia during pegylated IFN-alpha2b plus ribavirin treatment for chronic hepatitis C: ribavirin is not always the culprit.

A 53-year-old woman admitted to our department for histologically proven chronic hepatitis C had previously been treated with pegylated interferon-alpha2b (PEG-IFN) plus ribavirin. Combination therapy had been withdrawn after 5 weeks because of severe anemia (hemoglobin 8.2 g/dl) despite a reduction in ribavirin dose. A second liver biopsy showed moderate chronic hepatitis with portoportal and portocentral bridges (Ishak score: grading 14/18, staging 4-5/6). Consequently, the patient was retreated with 1.5 microg/kg body weight weekly PEG-IFN and 1000 mg/day ribavirin. Ribavirin was withdrawn about 3 months later because of anemia. After 1 month of PEG-IFN alone, hemoglobin had decreased further to reach 7.9 g/dl; consequently IFN was stopped. An elevated reticulocyte count, indirect bilirubin concentration, and lactic dehydrogenase (LDH) concentration, and a positive direct Coombs test (IgG3, C3d also for panagglutinant irregular antibodies on eluate) led us to diagnose autoimmune hemolytic anemia (AHA). The patient received 1 mg/kg body weight/day prednisone, and all parameters normalized within 20 days. This is the first case of IFN-related AHA during PEG-IFN plus ribavirin therapy. Physicians should be aware that PEG-IFN can be the cause of AHA during a ribavirin-containing regimen for chronic hepatitis C.

Anemia, Hemolytic, Autoimmune↗
PubMed1979

Erythrocytic ecdysis. An unusual morphologic finding in a case of sickle cell anemia with intercurrent cold-agglutinin syndrome.

Examination of peripheral blood smears from a patient with sickle cell disease during crisis associated with an upper respiratory tract infection, pneumonia, a positive Coombs test, and an elevated cold agglutinin titer revealed unique abnormalities associated with her erythrocytes, which have not been reported previously. In addition to the usual changes in peripheral blood occurring during crisis in sickle cell anemia, large numbers of free, filamentous forms that appeared to be derived from erythrocytes were present on repeated Wright's-stained smears. Erythrocytes were markedly distorted and had single and multiple surface protrusions that appeared to be antecedents of the free filamentous forms. Scanning electron microscopy confirmed the marked changes in the erythrocytes and revealed membrane alterations not apparent by use of the light microscope. It is suggested that the membrane stripping observed in this case was due to cold agglutinin--complement-mediated surface injury superimposed on the known abnormalities of the membranes of sickle erythrocytes.

Agglutinins↗
PubMedDate not supplied

Treatment of significant bacterial infections in adults with cefoxitin.

Cefoxitin is a new antimicrobial agent derived from cephamycin C. Fifty-four hospitalized patients with 63 clinically significant infections were treated with cefoxitin. Fifty-four infections (86%) were cured by therapy with cefoxitin alone or together with local therapy (i.e., heat, elevation, or surgical drainage). Six infections (10%) were not eradicated by the therapy used. Three patients could not be evaluated. Addition of oral probenecid therapy produced increases in levels of cefoxitin in serum and increased the inhibitory and bactericidal levels of cefoxitin in serum to more favorable ratios. Adverse side effects were seen in 19 patients and included positive direct Coombs' tests, increased eosinophil counts, skin rashes, vasculitis, phlebitis, elevation of liver enzymes, and drug-induced fever.

Adult↗
PubMedDate not supplied

Therapy of skin, soft tissue, and bone infections with cefoxitin sodium.

Twenty-seven patients with skin and soft tissue infections, including three with contiguous osteomyelitis, were given cefoxitin intravenously or intramuscularly; the infections of 25 (93%) were resolved with cefoxitin therapy. Etiologic agents included staphylococci, streptococci, Enterobacteriaceae, and anaerobes. Susceptible pathogens were inhibited by less than or equal to 8 micrograms of cefoxitin/ml. This level of drug was surpassed by mean peak serum concentrations eight- to 12-fold after intravenous infusions and two- to threefold after intramuscular injections and resulted in eradication of susceptible organisms from lesions during treatment. Intravenously administered cefoxitin was well tolerated, although eosinophilia, phlebitis, elevation of levels of hepatic enzymes, and a positive direct Coombs' test were observed. Intramuscular injections of cefoxitin in 0.5% lidocaine caused pain and induration and thus were poorly tolerated.

Abscess↗
PubMedDate not supplied

Serologic diagnosis of human brucellosis: analysis of 214 cases by agglutination tests and review of the literature.

The serum agglutination test (SAT) and 2-mercaptoethanol (2ME) agglutination were used in studies of the sera of 214 patients in whom brucellosis was suspected. On the basis of historical, epidemiologic, clinical, and serologic data, four groups were identified: group I (108 cases) had negative agglutination reactions, and brucellosis was considered unlikely; group II (57 cases) had positive agglutination reactions, and active brucellosis was diagnosed; group III (37 cases) had positive agglutination reactions, but other factors--notably, a history of prior infection--made inactive brucellosis likely; and group IV (12 cases) had positive agglutination reactions, but insufficient data were available for further classification. Most patients with active brucellosis had agglutinin titers of greater than or equal to 160; however, no single titer was always diagnostic. Although more sensitive tests are available, agglutination reactions provide data sufficient to differentiate active from inactive disease when other factors are considered and follow-up sera are tested. This article discusses individual cases and reviews the literature on the diagnosis of brucellosis.

Adolescent↗
PubMedDate not supplied

Cefotaxime therapy for patients with osteomyelitis and septic arthritis.

Cefotaxime, a new cephalosporin, was evaluated for efficacy and safety in the treatment of 52 patients with serious bone and joint infections. For five of these patients therapy could not be evaluated. Diagnosis of osteomyelitis or septic arthritis was made on the basis of clinical and roentgenographic evidence of infection. The diagnosis of a bone infection was confirmed by either a positive culture of a bone biopsy or of blood in combination with a positive bone scan or roentgenogram. The diagnosis of a joint infection was confirmed by a positive culture of joint aspirate samples. Osteomyelitis was arrested in 93% (15 of 16 patients) of cases of acute osteomyelitis, 89% (24 of 27 patients) of cases of chronic osteomyelitis, and 100% (4 of 4 patients) of cases of septic arthritis. Follow-up ranged from 0-17 months after completion of cefotaxime therapy. Laboratory monitoring revealed positive direct Coombs' test (six patients), neutropenia less than 1,000 polymorphonuclear leukocytes (two patients), macular rash (two patients), phlebitis (two patients), and pseudomembranous colitis (one patient). It is concluded that cefotaxime is a useful and safe antibiotic for the treatment of osteomyelitis and septic arthritis.

Adult↗
PubMed1983

Ceftazidime in severe infections: a Swiss multicentre study.

A total of 105 patients (mean age 57, range 15 to 90) with serious infections were treated with intravenous ceftazidime, usually 2 g 8-hourly. Most patients had complicating factors such as major surgery, cancer, chronic obstructive lung disease, catheters or anatomical abnormalities. Eighty-seven infectious episodes in 77 patients could be assessed for efficacy. Bacteraemia was diagnosed in 26% of these episodes. Seventy-five per cent of infections were due to Gram-negative bacteria, Pseudomonas aeruginosa being the most frequent. The major sites of infections were the lower respiratory tract (30), the urinary tract (28), the soft tissues (9), the biliary tract (4), bones (4) and the ears (4). Overall, 67% of the patients were cured, 20% improved, 7% relapsed and 6% failed to respond. Among the 27 infections due to Ps aeruginosa, only two failures (in the same patient) and four relapses were recorded. However, in the two failures and in three other cases with persistent Ps. aeruginosa colonisation, the organism had become resistant to ceftazidime. Three failures were recorded in the seven Staphylococcus aureus infections included in this study. Superinfection occurred in four patients. Adverse events included rash (6), Clostridium difficile toxin-induced diarrhoea (3), transaminase elevation (3), weakly positive Coombs test (10). Ceftazidime appears to be safe and effective for the treatment of severe Gram-negative infections, including those caused by Ps. aeruginosa.

Adolescent↗
PubMed1983

Open study of ceftazidime in serious infections due to multiply-resistant bacteria.

We treated 37 infections in 32 patients who had one or more significant underlying diseases. Most of the responsible micro-organisms were multiresistant, but were initially sensitive to ceftazidime. They included 16 Pseudomonas spp., 10 Serratia spp., 6 Klebsiella spp., 7 other Enterobacteriaceae, 3 Staphylococcus spp., 3 strict anaerobes and 1 Acinetobacter anitratus. Indications for ceftazidime encompassed a broad spectrum of diseases: 10 complicated UTI, 13 skeletal and soft tissue infections, 4 bronchopulmonary infections, 6 intra-abdominal infections, 3 septicaemias, 1 brain abscess with meningitis. Ceftazidime was administered without other antimicrobials, except for metronidazole in two patients with intra-abdominal abscesses. Doses varied from 2 to 12 g/day (median: 3 g), given for 3-31 days (median: 12 days). Clinical cure was recorded in 26 patients (81%), 24 (75%) having also a bacteriological cure. In six patients, clinical findings subsided significantly but with incomplete resolution or relapse during follow-up. Four organisms developed resistance during therapy: 2 Pseudomonas, 1 Enterobacter cloacae and 1 Bacteroides vulgatus. Three patients developed mild superinfections (2 Candida, 1 Staph. epidermidis). Ceftazidime was well tolerated; adverse events were mild and reversible. Local thrombophlebitis was observed twice, two patients had a positive reaction to the direct Coombs' test, two had transitory elevation of transaminases and one suffered from drowsiness during intravenous injections. Ceftazidime appeared to be a valuable weapon for fighting severe infections in compromised patients, especially when Gram-negative bacilli were involved.

Abscess↗
PubMed1986

The safety profile of imipenem/cilastatin: worldwide clinical experience based on 3470 patients.

The relative safety of imipenem/cilastatin for 3470 patients was reviewed to see if the safety profile was similar to that seen for the first 1723 patients treated. The most common clinical adverse experiences were local ones related to the site of intravenous infusion. Gastrointestinal adverse experiences included nausea, vomiting, or diarrhoea. The frequency of pseudomembranous colitis was low (0 X 1%). The most common central nervous system abnormality was seizure. The most common background factor was central nervous system abnormality including prior history of seizure. Dermatological adverse experiences included rash, pruritus and urticaria. Bleeding and decreased renal function were uncommon. The most common laboratory changes included transient increased liver function values, eosinophilia, positive Coombs' test (not associated with haemolysis) and increased platelets. The current clinical and laboratory safety data are similar to those obtained in the early part of the clinical trials.

Bacterial Infections↗
PubMed1987

A prospective randomized trial of ceftazidime versus cefazolin/tobramycin in the treatment of hospitalized patients with pneumonia.

Ceftazidime and cefazolin/tobramycin were compared in the treatment of hospitalized patients with pneumonia. Iv doses 8-hourly were: ceftazidime--2 g, cefazolin--1.5 g, tobramycin--1.7 mg/kg. For patients with pseudomonas infection randomized to cefazolin/tobramycin, ticarcillin (3 g iv 4-hourly) was used instead of cefazolin. One hundred and ten of 129 patients were evaluable (ceftazidime = 52, cefazolin/tobramycin = 58). Seventy five cases (68%) had documented pathogens of which 81% were aerobic Gram-negative bacilli. Analysis of clinical response showed no difference in overall results (P = 0.77), or separate outcomes: cured (P = 0.85), improved (P = 0.62), failed (P = 0.53), or relapsed (P = 0.50). No differences in bacteriological response were noted either: eradication (P greater than 0.10), elimination with recurrence (P greater than 0.10), persistence (P greater than 0.10). The incidence of enterococcal and fungal colonization and superinfection was the same for both regimens. There was a greater incidence of Coombs' test positivity with ceftazidime (P less than 0.01) but greater nephrotoxicity with cefazolin/tobramycin (P less than 0.02). Ceftazidime appears to be as efficacious as cefazolin/tobramycin in the treatment of hospitalized patients with pneumonia, and is less nephrotoxic.

Adolescent↗
PubMed1989

Preclinical safety studies of cefmetazole.

In order to assess the safety of cefmetazole, preclinical multiple-dose parenteral studies, varying from one to three months in length, were conducted in Sprague-Dawley rats and beagle dogs. Although the largest doses used were in multiples of several times the weight-adjusted doses intended for humans, cefmetazole was generally well tolerated. The principal adverse effect noted in the adult rats receiving the largest doses (2000 and 2500 mg/kg/day) of cefmetazole was slight elevation of serum alanine aminotransferase. Infant rats injected subcutaneously with 300 mg/kg/day or more of cefmetazole for 35 consecutive days had reversible reductions in testicular weight and maturation of spermatogenesis, but not lasting discernible effect on reproductive function. The most consistent effects of longterm multiple dosing with cefmetazole in dogs consisted of vomiting and retching during dosing and reversible haematological changes (mild regenerative anaemia, positive Coombs' test, clinically-silent thrombocytopenia) in a number of the dogs. These findings supported the interpretation that cefmetazole was acceptably safe for clinical studies in humans.

Animals↗
PubMed1998

Pure red cell aplasia and myasthenia gravis with thymoma: a case report and review of the literature.

A case of pure red cell aplasia (PRCA), myasthenia gravis (MG) and thymoma is reported. A 70-year-old woman presented with severe anemia. She had been diagnosed as having MG 8 years earlier and her symptoms were adequately controlled with ambenonium chloride. When she visited our hospital, her hematocrit was 13.7% with a hemoglobin concentration of 4.7 g/dl and her reticulocyte counts were persistently abnormal at 0.1%. Although both direct and indirect Coombs' tests were positive, there was no evidence of hemolysis. Routine screening tests for other etiologies of anemia were negative. Serological tests for anti-DNA and anti-acetylcholine receptor antibodies gave positive results. A bone marrow examination revealed severe erythroid hypoplasia. PRCA was diagnosed and the patient was treated with periodic transfusions. A lateral view chest roentgenogram and a computed tomography scan of the thorax showed the presence of an anterior mediastinal mass which was suspected to be thymoma. The patient underwent thymothymectomy and the tumor was diagnosed as a thymoma. Although the patient received no treatment for MG and PRCA after surgery, her hematological test results rapidly improved and she was discharged from the hospital on the 29th postoperative day. At that time, her hematocrit was 33.2%, her hemoglobin concentration was 10.0 g/dl, her peripheral reticulocyte level was 1.8% and her left partial ptosis had improved. She is doing well, 9 months after surgery. For a patient to remain in remission without treatment for PRCA and MG after thymothymectomy is extremely rare.

Aged↗
PubMed1994

Autoimmune haemolytic anaemia after ABO-match, ABDR full match kidney transplantation.

We report a case of autoimmune haemolysis after an ABO- and ABDR-identical kidney transplantation which leads to the discussion of the role of cyclosporin A (CsA). A 46-year-old woman with end-stage renal disease and no history of auto-immune disease received an ABO- and ABDR-identical first renal allograft from a cadaver donor. On day 16, while on a heavy sequential immunosuppressive regimen including anti-thymoglobulins, azathioprine (Aza), prednisolone (Pred) and CsA, she developed an autoimmune haemolysis with positive Coombs test, IgM+C type. Elution of antierythrocyte antibodies did not enable us to identify any specificity. Haemolysis lasted 45 days before haemoglobin slowly increased after CsA had been greatly reduced. Direct antiglobulin tests remained positive 5 months after transplantation and became negative the following month. Eight months after the transplantation the patient had a normal haemoglobin level and normal renal function. Although the typing of autoantibodies was not possible, our data suggest that this patient's haemolysis may be related to the clonal development of donor B lymphocytes in the recipient, favoured by an HLA A-B-DR identity and post-transplant CsA therapy, as exceptionally reported in the literature.

ABO Blood-Group System↗