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Hypothalamic proline-rich polypeptide is an oxidative burst regulator.

The AGAPEPAEPAQPGVY proline-rich polypeptide (PRP) was isolated from neurosecretory granules of the bovine neurohypophysis; it is produced by N. supraopticus and N. paraventricularis. PRP possesses immune-modulating activity, preventing the death of Gram-negative bacteria-infected mice. Here we show that PRP does not affect human peripheral blood neutrophlis and monocytes phagocytosis but dramatically enhances spontaneous or fMLP- and PMA-induced, and also phagocytosis-dependent, oxidative burst. We demonstrated the regulatory role of PRP on the oxidative burst induction of normal and relapsing inflammatory disease (Behcet's disease and familial Mediterranean fever) neutrophils and monocytes. Our results suggest a previously undescribed role for the hypothalamic peptide within primary activated neutrophils and monocytes, since we provide evidence that PRP can differentially regulate both chemotaxis- and phagocytosis-dependent oxidative burst in normal and inflammatory disease effector cells.

Adolescent↗

Risk factors assessment in fabrile neutropenia.

It is now established that febrile neutropenic cancer patients constitute a heterogeneous population with a variable risk for serious medical complication development. Optimal patient management should take that risk into account by replacing, for instance, the classical, in-hospital administered, broad-spectrum intravenous antibiotics by newer therapeutic approaches including oral and/or outpatient therapeutic strategies for the 'low-risk' patients. The development of such approaches which have been shown safe and feasible, implies the existence of universally accepted, validated and reliable clinical prediction rules for the identification of these low-risk patients. Some prognostic factors predicting the response to the empiric treatment, the development of a bacteremia, and the final outcome of a febrile neutropenic episode have been established (such as duration and profoundness of neutropenia, acute leukemia, administration of chemotherapy for treatment of relapse, high temperature, shock and/or chills, inpatient status at fever onset) and some models combining them have already been proposed, firstly by Talcott and coworkers and more recently by the Multinational Association for Supportive Care in Cancer (MASCC) study section on infections. The sensitivity of these rules as a selection tool for identifying patients at low-risk of complication, however, needs to be improved and we have to assess their clinical usefulness, safety and/or reproducibility better in order to allow a more adequate choice between the therapeutic strategies, to continue to improve patients quality of life and to optimize the cost-effectiveness of the treatments.

Anti-Bacterial Agents↗

Acute myelogenous leukemia in a donor after granulocyte colony-stimulating factor-primed peripheral blood stem cell harvest.

This article describes the first case of acute myeloid leukemia (AML) in a healthy donor at 14 months after granulocyte colony-stimulating factor (G-CSF)-primed peripheral blood stem cell (PBSC) harvest. In September 2001, a healthy 61-year-old female was given G-CSF prior to PBSC harvest for her brother with multiple myeloma. In spite of successful engraftment, the recipient died from a disease relapse. In November 2002, the donor, admitted with high fever and leukocytosis with 98.5% blastoid cells, was diagnosed as having AML (M1). Her leukemia cells were positive for CD13, CD33, and G-CSF receptor without chromosomal abnormality and responded to G-CSF in vitro. During chemotherapy, she died of progressive pneumonia. If our case is truly the first, the incidence of leukemia in donors may not be higher than that of naturally occurring leukemia. However, efforts towards an international long-term study, or at least to report every case similar to ours, would be required to be conclusive.

Female↗

Two cases of the nephrotic syndrome with a reversible coagulation defect.

Two cases of the nephrotic syndrome with an apparently identical defect of blood coagulation, discovered during preparation for renal biopsy are described. Plasma from both patients showed prolongation of thrombin and kaolin cephalin times which was probably due to abnormally slow polymerization of fibrin monomer. Corticosteroid therapy reversed the abnormal times in one case. One of the patients showed seasonal relapses which occurred in relation to episodes of hay fever associated with allergy to grass pollen. The other patient showed some similar features, but on renal biopsy was found to have proliferative glomerulonephritis.

Adult↗

[Acute suppurative thyroiditis in a patient with prior subacute thyroiditis].

Acute suppurative thyroiditis is an uncommon thyroid disorder usually caused by bacterial infection. The most common route of infection is a fistula that originates from the fundus of the pyriform sinus. Pre-existing thyroid disease, most commonly nodular goiter, has been reported to be present in acute suppurative thyroiditis. A 44 year old man presented a subacute thyroiditis, resolved by nonsteroidal antiinflammatory treatment. One year later, the patient abruptly complained of fever and painful swelling in the thyroid region. A relapse subacute thyroiditis was diagnosed and prednisone treatment was started. A few days later owing to a worsening of the pain and of the clinical features the patient was referred to our department. He presented dysphagia and he was feverish, the overlying skin of the neck swelling was erythematous and warm. There was a neutrophilia (83.7%). Plasma FT4, FT3 and TSH were normal. Anterior neck region ultrasonography showed an enlargement of the left thyroid lobe with poorly defined shapes and inhomogeneous parenchyma while the right lobe of the gland was normal. The 131-I thyroid scan showed a large cold area in the upper part of the left thyroid lobe and preserved radionuclide uptake in the residual parenchyma. The RAIU was normal. We diagnosed acute suppurative thyroiditis and started antibiotics treatment. The day after the patient was still feverish and he gave out from the mouth a great quantity of sero-purulent material with a swelling reduction and improvement of the neck pain. Barium swallow examination did not show any fistula in the cervical esophagus. The fistula opening was demonstrated by indirect laryngoscopy in the postero-lateral side of hypopharynx.(ABSTRACT TRUNCATED AT 250 WORDS)

Abscess↗

[Monoclonal antibody therapy with mabtera of patients with b-cell low grade non-Hodgkin's lymphoma].

The data on monoclonal antibody monotherapy (mabtera, rituximab) in 44 patients with B-cell low grade non-Hodgkin's lymphoma were assessed. Thirty-four of them had received several courses of second- or third line chemotherapy: mabtera was used as first-line therapy in 10. Mabtera was administered in a dose of 375 mg/m2 body surface, once a week, by slow intravenous infusion, 4-14 times depending on effect. Each relapsing patient received, on the average, 4 infusions, while each refractory one--8 weekly infusions. Overall response in the first group was 44%. Median overall relapse-free survival was 9 months. Apparenti effect of treatment was reported in 50% of primary patients (median overall relapse-free survival--15 months). Therapy was well tolerated. Fever and shivering stage I and II were among the most frequent post-infusion effects. High level of CD-20+B-lymphocytes should be used as prognostic indicator for effectiveness of therapy.

Adult↗

[The efficacy of and tolerance for fansimef in the treatment of tropical malaria in the south of the Socialist Republic of Vietnam].

The efficacy of and tolerance to fancimef in 49 patients was compared to the efficacy of and tolerance to quinine in combination with fansidar in 33 patients with moderate P. falciparum malaria. A good tolerance to and a high efficacy of fancimef have been shown, which was manifested in rapid fever arrest, disappearance of parasitemia, absence of the disease relapses, which were observed in 2 patients on quinine combined with fansidar. The advantage of fansimef is one-time administration of the total course dose.

Acute Disease↗

Efficacy and safety of pidotimod in the treatment of recurrent respiratory infections in children.

The activity of pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6) was evaluated in a double-blind, placebo-controlled, randomized, multicentre trial, on 120 pediatric patients affected by recurrent respiratory infections. The clinical course of acute infections was favourable both in placebo and in treatment group, but recovery was quicker with pidotimod than with placebo. Antibiotic therapy and time of hospitalization were shorter in the patients taking pidotimod, and main symptomatic parameters (pharyngalgia, dysphagia, mucous membrane inflammation, adenopathy, anorexia) receded quickly. In patients receiving the drug as well as in placebo group changes in laboratory parameters, indicating recovery from the acute infectious events, were observed. A significant trend to normalization of the immune response, evidenced by chemotaxis and leukocyte phagocytosis index, was found only in patients treated with pidotimod. A significant decrease in the risk of relapses was observed in patients treated with pidotimod (35%), as well as a reduction of hospitalization (86%) and a decreased antibiotic therapy (47%). If a relapse occurred, the response of treated patients was quicker (fever, antibiotic therapy, hospitalization). These findings allow to correlate the individual immune response activation to the resistance to recurrent infections and also to a better response to therapy in case of clinically relevant disease. No side effects were observed. Only in 12 patients (5 pidotimod, 7 placebo) mild reactions were observed, but they were attributed to concomitant antibiotic treatment or other factors. No alterations in main laboratory parameters were seen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗

Reduced blood transfusions requirements after allogeneic bone marrow transplantation: results of a randomised, double-blind study with high-dose erythropoietin.

Patients with haematological malignancies undergoing allogeneic BMT were randomised to treatment with recombinant human erythropoietin (rHuEPO) (n = 25) or placebo (n = 25). rHuEPO was given at 200 U/kg daily for 4 weeks and 200 U/kg twice weekly for a further 4 weeks. The groups were similar regarding several prognostic factors. There were no differences between the two groups regarding time to engraftment, fever, hospitalisation, GVHD, infections, haemorrhages, transplant-related mortality, relapse and survival. However, more patients in the control group had a raised serum creatinine (43% vs 14%; p = 0.04). Red blood cell (RBC) transfusion requirements for the first 2 months after BMT were significantly lower in the rHuEPO group compared with the control group (5 units vs 10; p = 0.04). Time to unsupported Hb > 70 g/l was less in patients treated with rHuEPO (14 days vs 24; p = 0.03). No effect was seen on platelet engraftment or the number of transfused platelet units. Two patients in the control group compared with none in the rHuEPO group became refractory to platelet transfusions. According to the protocol the study drug was reduced (Hb > 100) or discontinued (Hb > 120) for a mean of 3.6 weeks among 11 rHuEPO patients compared with 1.9 weeks among 7 controls (p = 0.02). Seven of the treated patients compared with none of the controls reached Hb > 120 during the study period (p = 0.004). Among the rHuEPO treated patients, EPO-levels were significantly higher than in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Disseminated intravascular coagulation in a case of adult onset Still's disease].

We report a 82-year-old woman with adult onset Still's disease (AOSD), who presented with high fever, skin rash, swollen axillary lymph nodes, accelerated erythrocyte sedimentation rate, leukocytosis, abnormal liver function tests, hypoalbuminemia, negative antinuclear antibody and rheumatoid factor, and lack of renal involvement. Disseminated intravascular coagulation (DIC) was also diagnosed on admission. An antipyretic relieved high fever and DIC soon improved. Three years later, AOSD relapsed accompanied by hypercoagulation and hyperfibrinolysis. The patient developed subdural hematoma and DIC due to a brain contusion. High titers of serum soluble adhesion molecules and soluble thrombomodulin were noted on the first episode of DIC. These findings indicated that endothelial cells were damaged in AOSD complicated by DIC.

Aged↗

[Comparative clinical and histological studies in the diagnosis of isolated proteinuria and hematuria].

In 311 patients with clinical suspicion to glomerulonephritis biopsies of the kidneys were performed. In these cases in 82% the histological or tentative diagnosis, respectively, of a glomerulonephritis could be made. As diseases preceding the glomerulonephritis relapsing tonsillitides are occupying the first place, whereas scarlet fever, otitides, furunculoses and sinusitides were observed more infrequently. Clinically cases of oligosymptomatic glomerulonephritis were more frequently observed than monosymptomatic ones. One fifth of the patients exhibited a restricted renal function or a proteinuria of 3 g/24 hours, in which case proliferatively sclerosing, diffusely proliferative and membranaceous forms occupied the first place.

Adolescent↗

Bacterial pericarditis: diagnosis and management.

Bacterial pericarditis occurs by direct infection during trauma, thoracic surgery, or catheter drainage, by spread from an intrathoracic, myocardial, or subdiaphragmatic focus, and by hematogenous dissemination. The frequent causes are Staphylococcus and Streptococcus (rheumatic pancarditis), Haemophilus, and M. tuberculosis. In AIDS pericarditis, the incidence of bacterial infection is much higher than in the general population, with a high proportion of Mycobacterium avium-intracellulare infection. Purulent pericarditis is the most serious manifestation of bacterial pericarditis, characterized by gross pus in the pericardium or microscopically purulent effusion. It is an acute, fulminant illness with fever in virtually all patients. Chest pain is uncommon. Purulent pericarditis is always fatal if untreated. The mortality rate in treated patients is 40%, and death is mostly due to cardiac tamponade, systemic toxicity, cardiac decompensation, and constriction. Tuberculous infection may present as acute pericarditis, cardiac tamponade, silent (often large) relapsing pericardial effusion, effusive-constrictive pericarditis, toxic symptoms with persistent fever, and acute, subacute, or chronic constriction. The mortality in untreated patients approaches 85%. Urgent pericardial drainage, combined with intravenous antibacterial therapy (e.g. vancomycin 1g twice daily, ceftriaxone 1-2g twice daily, and ciprofloxacin 400 mg/day) is mandatory in purulent pericarditis. Irrigation with urokinase or streptokinase, using large catheters, may liquify the purulent exudate, but open surgical drainage is preferable. The initial treatment of tuberculous pericarditis should include isoniazid 300 mg/day, rifampin 600 mg/day, pyrazinamide 15-30 mg/kg/day, and ethambutol 15-25 mg/kg/day. Prednisone 1-2 mg/kg/day is given for 5-7 days and progressively reduced to discontinuation in 6-8 weeks. Drug sensitivity testing is essential. Pericardiectomy is reserved for recurrent effusions or continued elevation of central venous pressure after 4-6 weeks of antituberculous and corticosteroid therapy.

Anti-Bacterial Agents↗

Treatment of visceral leishmaniasis in a patient with AIDS with antimony and gamma-interferon: remission and prevention of relapse by maintenance therapy with weekly pentamidine.

A 41-year-old AIDS patient with fever, nightly perspiration, diarrhoea, anaemia and leukopenia was diagnosed as having visceral leishmaniasis (VL). After 8 weeks of antimony treatment combined with gamma-interferon, given in 2 courses of 3 and 5 weeks, 12 weeks apart, the bone marrow revealed no parasites by microscopy and culture. Parasitic DNA could still be demonstrated by polymerase chain reaction. Weekly intravenous pentamidine maintenance therapy seemed to prevent relapses. Over time the patient was treated for disseminated M. avium infection, CMV retinitis, porphyria cutanea tarda and renal tubular acidosis. Ultimately he succumbed, 2.5 years after the diagnosis of VL and 4.5 years after the diagnosis of AIDS was established.

AIDS-Related Opportunistic Infections↗

Multiple myeloma presenting high fever and high serum levels of lactic dehydrogenase, CRP, and interleukin-6.

Two myeloma patients presented high fever with no signs or data indicating infection at diagnosis or relapse. Both patients had plasmablastic myeloma, and serum levels of lactic dehydrogenase (LDH) and CRP were extremely high. Plasmablastic morphology, high LDH, and CRP were recognized as poor prognostic factors, indicating a fulminant phase of multiple myeloma. Interleukin-6 (IL-6) was only high in measured cytokines. We proposed that IL-6 caused high fever and induced the fulminant phase in these 2 cases.

C-Reactive Protein↗

[The clinical and evolutional characteristics of visceral leishmaniasis in patients with HIV infection].

OBJECTIVE: To analyze the clinical features, yield of the diagnostic techniques, and therapeutic response of HIV-associated visceral leishmaniasis (VL), and compare the initial episodes to the relapses. METHODS: Forty-one episodes of leishmaniasis visceral, diagnosed in 31 HIV-positive patients between 1st February 1992 and 31st January 1996 were reviewed. RESULTS: The prevalence of VL in HIV-positive patients in our center was 4.2%. Fifty-eight percent of the patients had AIDS prior to the diagnosis of VL. Fever was more frequent in the initial episodes than in the relapses (90.3% versus 60%; p < 0.05; OR: 6.2; IC 95%: 0.8-51.5), splenomegaly was more frequent in the relapses (100% versus 71%; p = 0.05). The diagnostic delay was longer in the initial episodes (27.2 +/- 22.7 versus 5 +/- 4.8 days; p < 0.05). The diagnostic yield of bone marrow biopsy was 82.1%, of liver biopsy 72.7% and of splenic fine-needle aspiration 87.5%. The indirect immunofluorescence test for Leishmania antibodies was positive in 5.9% of cases. Therapeutic failure occurred in 47.6% of patients treated with antimonials and 3.3% of patients treated with amphotericin B. Those patients who received secondary prophylaxis had less relapses than those who did not (17.6% versus 66.7%; p < 0.05; OR: 0.11; IC 95%: 0.01-1.28). Of the 31 patients, twenty-six (83.8%) died, and in none of them was the cause of the death directly related to LV. CONCLUSION: HIV-associated VL manifests clinically in a similar fashion to the immunocompetent's disease. It appears in advanced immunosuppression phases, behaving like other AIDS-defining illnesses. In spite of a good therapeutic response the relapse rate is high.

AIDS-Related Opportunistic Infections↗

Effective duration of antimicrobial therapy for the treatment of acute lobar nephronia.

OBJECTIVE: Effective treatment of acute lobar nephronia (ALN) can prevent its progression to renal abscess. The goal of this prospective study was to compare the treatment efficacy for pediatric patients who had ALN with a 3- vs 2-week intravenous plus oral antimicrobial-therapy regimen. METHODS: Patients who were suspected of having an upper urinary tract infection underwent a systematic scheme of ultrasonographic and computed tomographic (CT) evaluation for ALN diagnosis. Patients with positive CT findings were enrolled and randomly allocated with serial entry for either a total 2-week or a 3-week antibiotic treatment regimen. Antibiotics were changed from an intravenous form to an oral form 2 to 3 days after defervescence of fever. Follow-up clinical evaluations and urine-culture analyses were performed 3 to 7 days after cessation of antibiotic treatment. Patients with persistent infection or relapse were considered as treatment failures. RESULTS: A total of 80 patients with ALN were enrolled. Forty-one patients were treated with a 2-week antimicrobial protocol, and the other 39 patients were treated with a 3-week course. Seven treatment failures, 1 persistent infection, and 6 infection relapses were identified, all of which were in the 2-week treatment group. Prolonged fever before admission and positive Escherichia coli growth (>10(5) colony-forming units per mL) in urine culture were noted as risk factors for treatment failure. All treatment failures were managed successfully with an additional 10-day antibiotic course. CONCLUSION: A total of 3 weeks of intravenous and oral antibiotic therapy tailored to the pathogen noted in cultures should be the treatment of choice for pediatric patients with ALN.

Acute Disease↗

Experience with ofloxacin in enteric fever.

Ofloxacin 200 mg b.i.d. for 8 days was employed in 28 patients with enteric fever with a positive blood culture. All patients were cured clinically and bacteriologically. The fever subsided within a mean of 3.1 days (range 1.6.5.3). No relapse, clinical or bacteriological, was observed when patients were followed up for 12 weeks.

Administration, Oral↗

[Bone marrow necrosis as a manifestation of leukemic relapse in a patient with bone marrow transplant].

A case of bone marrow necrosis (BMN) in transplanted acute lymphoblastic leukaemia (ALL) is presented. The propositus is a 16 year-old boy with L-2 type ALL on whom allogeneic bone marrow transplantation (BMT) had been performed after the second relapse. He was admitted to hospital at 415 after BMT with fever, malaise and hip pain. One week later he had aplasia without blast cells. Scanty cellularity with necrobiosis was found in bone marrow aspirates; bone marrow biopsy confirmed the suspicion of BMN. Osseus scintigraphy with 99-Tc-diphosphonate showed poor, irregular distribution. Steroid therapy was followed by a favourable response. Peripheral blast cells appeared two weeks later, and the relapse was confirmed by bone marrow aspiration. Chemotherapy was started, but the patient died on day 467 after BMT. BMN has been reported in ALL at onset, in relapses, after chemotherapy and as necropsy finding; however, it had not been found in patients subjected to BMT. The experience of these Service was revised, this being the only case of 140 patients subjected to BMT who presented such severe complication.

Adolescent↗