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Disseminated infection due to Encephalitozoon cuniculi in a patient with AIDS: case report and review.

OBJECTIVE AND METHODS: Infections due to microsporidia are increasingly recognized as opportunistic infections in patients with AIDS. We describe here a case of disseminated infection due to Encephalitozoon cuniculi and review the literature on this microsporidial infection. RESULTS: All 12 patients reported in the literature had AIDS and nine presented with disseminated infection involving the kidneys, sinuses, lungs, brain and conjunctiva. Asymptomatic infection was seen in three patients. Microsporidia were detected by light microscopy examination of urine samples in all the cases. Species identification was performed by various genotypic methods or transmission electron microscopy. Eight of 12 patients who received albendazole therapy experienced clinical improvement with documented clearance of spores in five of these eight patients. Two patients relapsed. CONCLUSIONS: E. cuniculi infection should be considered in severely immunocompromised HIV-infected patients with multi-organ involvement and fever, especially when renal failure is present. Microsporidial spores are usually seen in urine samples and in the involved organ. Albendazole therapy seems to be effective.

AIDS-Related Opportunistic Infections↗

Aetiology and pathogenesis of thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome: the role of von Willebrand factor-cleaving protease.

Thrombotic thrombocytopenic purpura (TTP) and haemolytic uraemic syndrome (HUS) are today often regarded as variants of one syndrome denoted as TTP/HUS, characterized by thrombocytopenia caused by intravascular platelet clumping, microangiopathic haemolytic anaemia, fever, renal abnormalities and neurological disturbances. Unusually large von Willebrand factor multimers have been observed in plasma from patients with chronic relapsing forms of TTP. Their appearance in patients with classic TTP is caused by deficiency of a specific von Willebrand factor-cleaving protease. A constitutional deficiency of this protease has consistently been found in familial cases of TTP, whereas in acquired TTP the protease deficiency is caused by the presence of an inhibiting autoantibody. A normal activity of von Willebrand factor-cleaving protease has been established in patients with HUS. In this chapter, we report 23 cases with severe constitutional protease deficiency: about one half of these patients had their first acute episode as children, whereas the other half had their first TTP event at an adult age, several of them during their first pregnancy. Two of these 23 individuals with congenital protease deficiency, both older than 35 years, have never had an acute TTP event. These results indicate that a deficiency of von Willebrand factor-cleaving protease alone is not sufficient to cause acute TTP. Patients with long-lasting dormant protease deficiency have been found to experience multiple relapses of TTP after having had their first acute episode. In one protease-deficient, plasma-dependent patient with chronic relapsing TTP, we estimated that 5% of normal protease activity is sufficient to remove the most adhesive von Willebrand factor multimers and prevent the formation of platelet microthrombi. The deficiency of von Willebrand factor-cleaving protease is a very strong risk factor for TTP, but the development of an acute bout requires a trigger, possibly causing the activation or apoptosis of endothelial cells in the microcirculation. It is unclear whether anti-endothelial cell antibodies, cytokines or other agents are involved in triggering thrombotic microangiopathy. The release of platelet calpain (and/or other proteases), leading to a degradation of von Willebrand factor and to platelet aggregation, has been reported in patients during their acute TTP episode. It is unknown whether calpain directly triggers an acute event or whether it merely reflects its release during the aggregation of platelets by the unusually large von Willebrand factor multimers. With regard to the heterogeneous aetiology of thrombotic microangiopathies, requiring distinct therapeutic measures, a new classification of thrombotic microangiopathy should replace the current, frequently inappropriate clinical discrimination between TTP and haemolytic uraemic syndrome.

ADAM Proteins↗

Septic arthritis as a late complication of carcinoma of the breast.

OBJECTIVES: To see if a past history of radiation therapy is a risk factor for septic arthritis. METHODS: We retrospectively searched our records of 282 patients with septic arthritis and found 10 cases of septic arthritis post-radiotherapy, all in females. We analysed our group, correlating them with the literature. We also compared our patients with a group of septic arthritis patients without radiation therapy. RESULTS: Nine had had radiation therapy for carcinoma of the breast. The shoulder joint was involved in six and the sternoclavicular joint in three. The tenth patient had had brachytherapy and radiation for carcinoma of the cervix and presented with septic arthritis of the hip. The mean age of the patients was 69 yr (49-82 yr). The mean time elapsed since radiation was 16 yr (3-34 yr). Twenty-three cases of shoulder septic arthritis in patients without past radiation therapy were selected for comparison. The five patients with past radiation therapy had fever less often and a longer time lapse before diagnosis. They required longer antibiotherapy. However, this prevented neither bone destruction nor relapse. CONCLUSIONS: In our study, a past history of radiation therapy was observed in 6/50 infections of the shoulder, 3/5 infections of the sternoclavicular joint, 6/23 cases of septic arthritis of the shoulder and all cases of septic arthritis of the sternoclavicular joint for females. Radiation therapy seems to be a risk factor for septic arthritis. Diagnosis would be aided by a greater awareness of the clinical and radiological features of this septic arthritis.

Aged↗

Use of rituximab, the new FDA-approved antibody.

Rituximab (Rituxan; IDEC Pharmaceuticals, San Diego, CA) is the first monoclonal antibody approved by the US Food and Drug Administration for the treatment of cancer. It is a genetically engineered chimeric (murine-human) monoclonal antibody (mAb) directed against the CD20 antigen found on the surface of normal and malignant B cells. Multicenter studies have demonstrated its efficacy against relapsed low-grade and follicular non-Hodgkin's lymphoma (NHL). The mAb demonstrated tolerable side effects, primarily limited to fevers and chills associated with the first infusion. The currently recommended dosage is 375 mg/m2/infusion, given weekly for 4 weeks. Because of its human component, rituximab has low immunogenicity and should not significantly hinder future retreatment. Future studies will evaluate the antitumor activity of rituximab combined with various other chemotherapeutic or biologic agents in the treatment of B-cell lymphoma and other CD20-positive lymphoid neoplasms.

Antibodies, Monoclonal↗

Penicillin-resistant Streptococcus mitis as a cause of septicemia with meningitis in febrile neutropenic children.

PURPOSE: The purpose of this report is to emphasize the importance of occurrence of Streptococcus mitis meningitis in febrile neutropenic children with hematopoietic malignancy. PATIENTS AND METHODS: Symptoms of meningitis and sepsis (fever, headache, changes in mental status) were seen in three patients who were severely neutropenic and undergoing cytotoxic chemotherapy for CNS relapse of their underlying malignancy (acute lymphoblastic leukemia (ALL), n = 2; Burkitt's lymphoma, n = 1). Chemotherapy had included cytosine arabinoside administered 7-14 days prior to presenting with sepsis and meningitis. All three patients had buccal mucositis or sinusitis. Blood cultures and CSF cultures showed S. mitis resistant to penicillin but sensitive to vancomycin. Vancomycin, at a dosage of 60 mg/kg/day to maximize CNS levels of antibiotic, was administered to all three children. RESULTS: Two of the patients recovered from S. mitis meningitis; recovery was associated with an improvement in their peripheral granulocyte counts. One patient, who remained neutropenic, died despite being treated with both intravenous and intraventricular vancomycin. CONCLUSION: Physicians caring for patients who are neutropenic and febrile need to be aware of the risk of meningitis occurring with S. mitis sepsis. Early treatment with high dosages of vancomycin (60 mg/kg/day) and an attempt to limit the duration of neutropenia are important factors in the outcome of such patients.

Bacteremia↗

GM-CSF and low-dose cytosine arabinoside in high-risk, elderly patients with AML or MDS.

Priming of leukemic cells with cytokines may enhance the efficacy of cell-cycle chemotherapy. In this study, we utilized these synergistic effects of granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim [Leukine]), hydroxyurea, and low-dose cytosine arabinoside to treat elderly patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS). In a single-institution, retrospective study, we evaluated 94 treatments with concomitant hydroxyurea, cytosine arabinoside, and GM-CSF between the years of 1997 and 2003 in high-risk elderly patients with AML or MDS. A total of 80% of patients received all of the GM-CSF doses; 78% of patients received all of the cytosine arabinoside doses. Adverse events were minimal. No patient developed mucositis or alopecia. The most common adverse event was neutropenic fever, which was noted in 57% of patients. Twenty-one percent of patients remained neutropenic after treatment until death or relapse. Sixty-eight percent of patients reached an absolute neutrophil count of greater than 1000 microL in a median of 33.5 days. Our data show an overall response rate of 52%, with a complete response rate of 39% and a partial response rate of 13%. Overall, our study showed that low-dose cytosine arabinoside given by continuous infusion together with continuous infusion GM-CSF and hydroxyurea was well-tolerated and effective in treating elderly AML and MDS patients who were not eligible for standard induction therapy.

Adult↗

Efficacy and safety of halofantrine in Pakistani children and adults with malaria caused by P. falciparum and P. vivax.

One hundred two patients aged 2-43 years diagnosed with acute malaria due to P. falciparum or P. vivax were treated with 3 doses of halofantrine (500 mg for > or = 18 year old patients and 8 mg/kg of patient body weight for 2-17 year olds), with each dose administered once in 6 hours and followed up for 28 days. Out of 102 patients 63 had P. falciparum, 36 had P. vivax and 3 had unidentified species. Following three dose therapy, 96.1% (98/102) of patients were cured, 0.98% (1/102) showed improvement from baseline, 1.96% (2/102) did not respond and were considered as treatment failures and one patient had indeterminate data. The lone patient, who relapsed after 120 hours post dose 1, was cured following re-treatment on day 7. The median parasite clearance and fever clearance times, from the first dose, were 26 hours and 30 hours, respectively. Eleven point eight percent (12/102) of patients reported adverse events, of which abdominal pain, reported by one subject, was considered to be probably related to the drug and required corrective therapy. There were no serious adverse events or fatalities and none of the patients had a change in QTc interval greater than 10%. Thirteen point seven percent (14/102) of patients had abnormal clinical laboratory parameters that normalized later.

Adolescent↗

[Benign paralysis of the 6th cranial nerve in children].

Acquired sixth nerve palsies in infants and children that occur without fever primarily suggest a tumor or intracranial hypertension. In a few instances, the cause is benign and spontaneous recovery occurs although relapses are occasionally seen. We report seven episodes of benign sixth nerve palsy in four children aged 5 1/2 months to 8 1/2 years. An ENT infection was the precipitating factor in four of these seven episodes. Recovery consistently occurred within 4 days to 6 weeks. None of the children had residual oculomotor impairment. The various etiologic hypotheses put forward in the literature are discussed. No study provides a pathophysiologic explanation for these transient palsies.

Abducens Nerve↗

[Liver damage following clomethacin treatment. 6 cases, including 2 deaths (author's transl)].

The authors report on 6 cases of severe liver damage following clomethacin treatment. Three patients developed prolonged hepatitis, lasting more than 3 months, with biochemical and histological signs of activity; one patient committed suicide by overdosage and died of subacute necrotizing hepatitis; one patient died of chronic cirrhotic hepatitis after prolonged clomethacin-alpha-methyldopa combined treatment, and there was one case of active hepatitis on latent cirrhosis. Drug toxicity was suggested by the presence of jaundice with occasional fever, urticaria or pruritus and eosinophilia, and by the lack of any other cause. It was confirmed in 3 cases by relapse of the condition after re-introduction of the drug, in one case by the circumstances surrounding death (attempted suicide) and in one case by the deterioration observed with increased dosage. In one patient the responsibility of clomethacin was shared with alpha-methyldopa, a potentially hepatotoxic drug.

Acute Disease↗

Experience of varicella vaccination in acute lymphoplastic leukaemia.

Varicella is a common benign childhood illness. Rarely, serious complications arise. Immunocompromised patients usually suffer a more serious form of the illness. It is therefore prudent to prevent the infection in this group of patients. Varicella vaccination has been proven by several workers to be effective in both healthy children and adults as well as in leukaemic children. As the vaccine had not been licensed for sale in Singapore, we could only import 10 doses of the vaccine under special license. This was given to 8 leukaemic children. Of this, 5 seroconverted after the first dose. Two patients had the benefit of a repeat vaccination 3 months later. Both subsequently seroconverted. Two of the patients died from a relapse of the illness, a year and 2 years after the vaccination. None of the patients developed any side effects of fever and pain or varicella or zoster after the immunisation even though there was close contact with chicken pox. Although the study sample was small, it appeared that the vaccine was safe and efficacious in leukaemic children, especially after a 2-dose injection.

Chickenpox↗

Paget's disease of bone: benefits of neridonate as a first treatment and in cases of relapse after clodronate.

This study assessed the efficacy of 200 mg of aminohexane bisphosphonate (neridronate) administered by intravenous infusion in a single dose or in two separate doses on consecutive days in 32 patients (16 males and 16 females, average age 66 years) affected by active Paget's disease of bone. Fifteen patients had never been treated with any antiresorptive agent and 17 had had unsatisfactory results from a prior clodronate treatment. All of the latter patients had failed to enter a remission stage (i.e., normalization of bone turnover was not reported at any time during treatment) and had had a full relapse within 6 months after clodronate infusion. In the present study bone-specific alkaline phosphatase (bAp), deoxypyridinoline (dPyr), and N- and C-terminal polypeptide of collagen type 1 (Ntx, Ctx) were determined before neridronate administration and at 1, 3, 6, and 12 months thereafter. Basal values of bAp were 51.7 +/- 2.3 microg/L, range 31.7-92.5 (normal range 6.2-23.6). No statistical differences in markers of bone turnover were evident in the basal state between new pagetic patients (bAp = 55.1 +/- 4.1) and those suffering a relapse after clodronate (bAp = 48.8 +/- 2.6). Neridronate induced an average percent change from baseline in excess bAp of 68.0 +/- 4.3 and in excess dPyr, Ntx, and Ctx of 68.1 +/- 11, 60.6 +/- 8.5, and 86.7 +/- 7.8, respectively. Markers of bone resorption declined more slowly in patients treated previously with clodronate, although the average change in percent decrement from baseline in excess bAp as well as in excess of bone resorption markers was not different from that registered in untreated pagetic patients. Response to treatment, defined as a percent decrement from baseline in excess bAp of 50% or more at any time during the 12-month follow-up, was observed in 27 patients (84.4%). Remission (a drop in bAp to within normal range) was achieved in 21 patients (65.6%) and was maintained in 12 at 12-month follow-up, with no significant differences between either 1- or 2-day infusions, or between new pagetic patients and those relapsing after clodronate. In 15 of 21 patients requiring analgesics to alleviate bone pain, pain was reduced or completely alleviated in 8. A slight, short-lived acute phase reaction (fever and/or arthromyalgia) occurred in 6 patients. To summarize, 200 mg of intravenous neridronate, in one or two doses, significantly reduced the biochemical indices of disease activity in the majority of patients, showing a normalization of bAp in more than 60%. We conclude that neridronate can be used safely in the treatment of patients with Paget's disease of bone either as a first bisphosphonate treatment or as retreatment for patients relapsing after clodronate.

Acute-Phase Reaction↗

A patient with bilateral primary adrenal lymphoma, presenting with fever of unknown origin and achieving long-term disease-free survival after resection and chemotherapy.

Primary adrenal lymphoma is extremely rare. We describe a 64-year-old female patient who presented with fever of unknown origin. Imaging studies demonstrated bilateral bulky adrenal masses. She underwent bilateral adrenalectomy and the pathological diagnosis was large cell immunoblastic (B-cell) lymphoma. She received adjuvant combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone in the following 6 months. She has been relapse free for 52 months. To the best of our knowledge, this case has the longest disease-free survival among those reported. The present case indicated that primary adrenal lymphoma should be included in the differential diagnosis of fever of unknown origin and/or suprarenal mass. Chemotherapy following surgical resection may be considered the treatment of choice.

Adrenal Cortex↗

[Relapsing polychondritis and mesenteric panniculitis: apropos of 2 cases].

We report two cases of polychondritis associated with mesenteric panniculitis. Case 1. In February 1989, a woman born in 1949 presented with 40 degrees C fever accompanied by pain in the abdomen and pelvis. Eight days later, nodular skin lesions appeared on her lower limbs. The abdomen was swollen with gas and undepressible. An abdominal CT scan revealed partitioned peritoneal collections, and a guided needle aspiration produced a chylous fluid. Direct and indirect bacteriological examinations gave negative results. Histology showed intense inflammatory reaction with giant cells and lipophages, thereby confirming the presence of mesenteric panniculitis. Six months later, the development of chondritic lesions on the nose and the helix of the ear clinched the diagnosis of polychondritis. The patient was put on corticosteroid therapy for a few months, and in January this year (1993) she is durably asymptomatic. Case 2. In October 1977, a woman born in 1937 presented with polychondritis with prolonged fever, inflammatory syndrome and chondritic lesions of the nose, larynx and helix of the ear. In December 1978, she developed signs of abdominal obstruction. Laparotomy revealed infiltration by multiple nodular formations of the entire posterior line of attachment of the mesentery. Biopsies withdrew a puriform fluid. Histology showed a partly necrotic adipose tissue with giant cells and lipophages. High-dose corticosteroid therapy partially controlled the chondritic and abdominal manifestations. The occurrence of abdominal pain in patients with polychondritis may result from several disorders, such as iatrogenic complications, digestive tract vasculitis or ulcerative colitis, but also associated mesenteric panniculitis.

Abdomen, Acute↗

[Successful treatment after acute promyelocytic leukemia (APL) syndrome of relapsed API with arsenic trioxide].

A 52-year-old female was diagnosed with relapsed APL in 2000. After obtaining informed consent, we administered 10 mg/day of arsenic trioxide intravenously. The complications were vomiting, increased transaminase and ATRA syndrome which included high fever, retention of body fluid, pleural effusion, pericardial effusion and respiratory failure from day 16. Administration of steroid and low dose chemotherapy (DNR 60 mg x day 1-2, BH-AC 250 mg x day 1-2) with arsenic was effective for APL syndrome, and complete remission (CR) was obtained at day 35 and PML-RAR mRNA became negative. After obtaining CR, consolidation chemotherapy was conducted and the patient was maintained the CR for more than 18 months. Although arsenic trioxide may be effective for relapsed APL, sufficient caution is needed because of the possibility of various complications.

Antineoplastic Agents↗

Phase II study of bisantrene in relapsed/refractory acute non lymphoid leukemias (ANLL).

The antileukemic activity of Bisantrene, a new anthracene derivative, has been evaluated in a phase II clinical study in 10 patients affected by refractory or primary relapsed ANLL. The patients received an induction course consisting of 250 mg/m2/day for 7 days followed, in case of CR, by 250 mg/m2/day for 3 days (consolidation treatment). In case of partial response a reinduction course (250 mg/m2/day for 3 days) was administered. Four out of the 10 patients obtained CR (3 of them after a single induction course). No significant toxic effect was noticed, apart from fever (due to myelosuppression) and hypotension in one patient who soon recovered without residual effects. These preliminary results could suggest further evaluation of Bisantrene in association with other drugs in both relapsed patients and those at onset of the disease.

Adult↗

Bronchial atresia with relapsing pulmonary infection in a middle-aged man.

Congenital bronchial atresia (CBA) is a rare disorder, first reported in 1953. Less than 100 cases are reported in the literature, mostly in young, asymptomatic male patients with involvement of the apical-posterior segment of the left upper lobe. Patients may complain of fever, cough, or shortness of breath, symptoms that result from post-obstructive, sometimes recurrent, infections. Chest radiography and computed tomography reveal a tubular branching density representing mucus impaction or mucocele with surrounding focal hyperinflation. Surgical excision is reserved for symptomatic cases. We report an unusual case of CBA in a middle-aged man with a history of relapsing infections, who was found to have an atretic superior segment of the left lower lobe, with surrounding areas of organizing pneumonia.

Activities of Daily Living↗

Sequential high-dose alkylating therapy and stem cell support for high-risk stage III breast cancer.

Patients who receive neoadjuvant chemotherapy for locally advanced breast cancer and have four or more ipsilateral axillary lymph nodes involved at surgery are at high risk for recurrence, with a median time to relapse of 18 months. We offered such patients high-dose chemotherapy with stem cell rescue. Patients received cyclophosphamide or paclitaxel and granulocyte colony-stimulating factor (G-CSF) to mobilize stem cells. Melphalan 140 mg/m2 was then given with stem cell rescue. Twenty-four to 35 days later, thiotepa 900 mg/m2 was given with stem cell rescue. Patients with hormone receptor-positive tumors received tamoxifen. We treated 14 patients in this fashion from 1995 to 1998. The mean age was 46.7 years. The majority of cancers were stage IIIB (79%). Thirteen women underwent mastectomy after anthracycline-containing chemotherapy and 50% had more than seven positive lymph nodes. Hospitalization was principally for neutropenic fever. Other morbidities were pneumonitis, cardiomyopathy, and grade 3/4 white blood cell (WBC) toxicity. No patient died of a treatment-related complication. Seven of 14 relapsed at 10, 12, <15, 15, 17, 21, and 36 months, with median follow-up of 26.5 months. Time to relapse in this small series is only modestly improved over historical experience with standard-dose adjuvant chemotherapy. Alternative strategies for treating locally advanced breast cancer should be pursued.

Adult↗

Comparative clinical trial of amoxycillin and chloramphenicol in the treatment of typhoid in adults.

A randomized clinical trial in sixty-two adult patients suffering from typhoid fever, proved by blood and marrow culture, showed that amoxycillin in a dosage schedule of 1 g 8-hourly orally for fourteen days was better than chloramphenicol with regard to clinical and temperature response and in respect of carriers and relapse rates. One patient developed a hypersensitivity reaction to amoxycillin which cleared on withdrawal of the drug. Success was achieved in 90% of cases. These findings lend very strong support to the value of amoxycillin as a superior alternative to chloramphenicol in the treatment of typhoid fever.

Adolescent↗