Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We carried out a multiple-center study, including a double-blined randomized clinical trial on fluconazole (Flu, group A) and ketoconazole (Keto, group B) and an open trial on Flu only for evaluating the efficacy and safety of Flu in treating deep and shallow fungal infection. 222 patients participated in the study and most of them had severe underlying diseases. The dosage and therapeutic duration were as follows: Flu 200-400 mg daily for 1-8 weeks in 34 patients with fungal infection and 150 mg as a single dose in 30 patients with fungal vaginitis; Keto 400 mg daily for 1-8 weeks in 30 patients with fungal diseases and for 5 days in 30 patients with fungal vaginitis. In the trial 124 patients were randomized to receive either Flu (64 patients) or Keto (60). The cure rate in group A and B was 81.3% (52/64) and 58.0% (35/60) respectively (P < 0.05). The fungal eradication rates of the two groups were 85.7% and 70.0% (P > 0.05) respectively. 98 patients entered the open trial. They included fungal infection of the respiratory tract and urinary tract, cryptococal meningitis, fungal sepesis and systemic dissemination of mycosis and fungal vaginitis. 84 (85.7%) were cured. The fungal eradication rate of this group was 92.9%. The side-effect rates of the three groups were 3.1% (2/64), 5.0% (3/60) and 6.1% (6/98) respectively. They were mild and transient vomiting, nausea, and anorexia. In group B and the open group however, there was one case of ALT elevation in each group (P > 0.05). This study suggests that Flu is a safe, effective and useful drug for the treatment of severe fungal infection.
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PMID:[Fluconazole versus ketoconazole in systemic fungal infection: a double-blind randomized study]. 1037 74

Disseminated aspergillosis is an uncommon and unpredictable complication in severely immunocompromised patients and poses a challenging problem in the management and care of seriously ill patients receiving intensive care therapy. We report an autopsied case of disseminated aspergillosis occurring ina 31-year-old female patient who was treated for HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. She initially presented with edema and proteinuria at a pregnancy check-up. At gestational age 33 weeks and 2 days, she had right lower abdominal pain, nausea, and jaundice. The next day she delivered a male neonate transvaginally, followed by excessive postpartum uterine bleeding. Although an emergency hysterectomy was performed, her hemorrhagic diathesis could not be controlled even after transcatheter embolization of the internal iliac arteries with subsequent ligation and repeated blood transfusions totalling to 31,070 ml. She eventually died of a cerebral hemorrhage 21 days after the parturition. Autopsy showed generalized jaundice and petechiae, as well as extensive hemorrhage observed in the abdominal wall, peritoneal cavity, and retroperitoneal and pelvic spaces. In addition,there were multifocal hemorrhages found in the left temporal, right frontal and posterior lobes of the cerebrum, and pons. Disseminated aspergillosis was found in the lungs, trachea, brain, esophagus, stomach, heart, and thyroid gland. These findings suggest that systemic postoperative complications, associated with massive blood transfusions and hepatic failure, mutually contribute to the overall deterioration of host defense mechanism, and may underlie the occurrence of devastating systemic fungal infection.
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PMID:[An autopsy case of HELLP syndrome with disseminated aspergillosis]. 1077 21

We conducted an open label, randomised clinical trial to compare amphotericin B colloidal dispersion (ABCD, Amphocil) 2 mg/kg/day intravenously with fluconazole 200 mg/day orally, for the prevention of fungal disease in neutropenic patients with haematological malignancies. In the event of unresolved fever after 4 days of empirical antibacterial therapy, patients in both treatment groups were to receive ABCD, 4 mg/kg/day. However, the study had to be stopped in an early phase, due to severe side-effects of ABCD. A total of 24 patients were enrolled, 12 patients were randomly assigned to receive prophylactic ABCD, which was administered for a mean of 13.9 days. Fluconazole prophylaxis was given to 12 patients for a mean of 21.2 days. Therapeutic ABCD, 4 mg/kg, was initiated in four patients because of suspected fungal infection, all of whom had initially received fluconazole. A high rate of infusion-related toxicity of ABCD was observed. Chills occurred in 15/16 ABCD recipients (94%), accompanied by a temperature rise of >/=2 degrees C in 4/16 patients and of >/=1 degrees C but <2 degrees C in 10/16 patients. Other ABCD-related adverse events were hypotension (4/16), nausea with vomiting (5/16), tachycardia (7/16), headache (3/16) and dyspnoea (3/16). For premedication patients received: antihistamines (12/16), hydrocortisone (9/16) and/or morphine (6/16). ABCD was discontinued in 8/16 patients (50%) due to side-effects, which ultimately dictated early termination of the study. We conclude that ABCD is not suitable for antifungal prophylaxis in neutropenic patients due to severe infusion-related side-effects. Subject numbers were too low for conclusions on variables of antifungal efficacy.
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PMID:Amphotericin B colloidal dispersion (Amphocil) vs fluconazole for the prevention of fungal infections in neutropenic patients: data of a prematurely stopped clinical trial. 1080 10

A 66-yr-old man with a history of squamous cell carcinoma and small cell carcinoma of the lung presented with nausea, vomiting, and abdominal pain. After passing black stools, he underwent upper endoscopy which showed gastric ulceration. A gastric brushing was performed which showed numerous nonseptate, ribbon-like hyphae with right-angle branching. The cytologic features permitted a diagnosis of a zygomycotic infection which was confirmed by histologic examination. Despite appropriate antifungal therapy, the patient expired. To the best of our knowledge, this is the first case of gastric zygomycosis diagnosed by brushing cytology. We believe that gastric brushing cytology allows for rapid diagnosis of zygomycotic mycoses, due to the distinctive morphology of these organisms; however, histologic examination is still required for assessment of invasion.
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PMID:Gastric zygomycosis diagnosed by brushing cytology. 1090 34

A Phase I dose escalation and pharmacokinetic study of the alkylating cytotoxic agent treosulfan was conducted to evaluate the maximum tolerated dose and the dose-limiting toxicities in patients with advanced malignancies rescued by autologous peripheral blood stem cell transplantation. Twenty-two patients (15 ovarian and 7 other carcinomas/lymphomas) with a median age of 48 years were treated with 28 high-dose courses. Treosulfan was infused over 2 h at escalating doses from 20 to 56 g/m2, and pharmacokinetic parameters were analyzed. At 56 g/m2, three of six patients experienced dose-limiting toxicities: diarrhea grade III/IV in three patients; mucositis/stomatitis grade III in one patient; toxic epidermal necrolysis in one patient; and grade III acidosis in one patient. Other low-grade side effects, including erythema, pain, fatigue, and nausea/vomiting, were recorded. Two patients died within 4 weeks after treatment because of rapid tumor progression and fungal infection, respectively. Plasma half-life, distribution volume, and renal elimination of treosulfan were independent of dose, whereas the increase in area under the curve was linear up to 56 g/m2 treosulfan. The maximum tolerated dose of high-dose treosulfan is 47 g/m2. A split-dose or continuous infusion regimen is recommended for future high-dose trials. In consideration of antineoplastic activity and limited organ toxicity, inclusion of high-dose treosulfan in combination protocols with autologous peripheral blood stem cell transplantation seems worthwhile.
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PMID:Clinical phase I dose escalation and pharmacokinetic study of high-dose chemotherapy with treosulfan and autologous peripheral blood stem cell transplantation in patients with advanced malignancies. 1110 34

Tinea capitis is a relatively common fungal infection of childhood. Griseofulvin has been the mainstay of management. However, newer oral antifungal agents are being used more frequently. A multicenter, prospective, randomized, single-blinded, non-industry-sponsored study was conducted in centers in Canada and South Africa to determine the relative efficacy and safety of griseofulvin, terbinafine, itraconazole, and fluconazole in the treatment of tinea capitis caused by Trichophyton species. The regimens for treating tinea capitis were griseofulvin microsize 20 mg/kg/day x 6 weeks, terbinafine [> 40 kg, one 250 mg tablet; 20-40 kg, 125 mg (half of a 250 mg tablet); < 20 kg, 62.5 mg (one-quarter of a 250 mg tablet)] x 2-3 weeks, itraconazole 5 mg/kg/day x 2-3 weeks, and fluconazole 6 mg/kg/day x 2-3 weeks. Patients were asked to return at weeks 4, 8, and 12 from the start of the study. Griseofulvin was administered for 6 weeks and the final evaluation was at week 12. Terbinafine, itraconazole, and fluconazole were administered for 2 weeks and the patient evaluated 4 weeks from the start of therapy. At this time, if clinically indicated, one extra week of therapy was given. There were 200 patients randomized to four treatment groups (50 in each group). At the final evaluation at week 12, the number of evaluable patients were griseofulvin, 46; terbinafine, 48; itraconazole, 46; and fluconazole, 46. Patients who discontinued therapy or were lost to follow-up were griseofulvin, 1/3; itraconazole, 0/4; terbinafine, 0/4; and fluconazole, 0/4. The causative organisms were Trichophyton tonsurans and T. violaceum species. Patients were regarded as effectively treated at week 12 if there was mycologic cure and either clinical cure or only a few residual symptoms. Effective treatment was recorded in, intention to treat, griseofulvin (46 of 50, 92.0%), terbinafine (47 of 50, 94.0%), itraconazole (43 of 50, 86.0%), and fluconazole (42 of 50, 84.0%) (p=0.33). Adverse effects were reported only in the griseofulvin group (gastrointestinal effects in six patients). Discontinuation from therapy due to adverse effects occurred only in the griseofulvin group (nausea in one patient). For the treatment of tinea capitis caused by the Trichophyton species, in this study, griseofulvin given for 6 weeks is similar in efficacy to terbinafine, itraconazole, and fluconazole given for 2-3 weeks. Each of the agents has a favorable adverse-effects profile.
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PMID:Therapeutic options for the treatment of tinea capitis caused by Trichophyton species: griseofulvin versus the new oral antifungal agents, terbinafine, itraconazole, and fluconazole. 1173 92

A 74-year-old man with diabetes mellitus type II, retinopathy and polyneuropathy suffered from exophthalmus, ptosis and diplopia. Magnetic resonance imaging and computer tomography showed a space-occupying process in the right orbital apex. An extranasal ethmoidectomy accompanied by an orbitotomia revealed the presence of septated hyphae. Aspergillus fumigatus was grown from the tissue. After surgical removal of the fungal masses, therapy with amphotericin B (1 mg kg(-1) body weight) plus itraconazole (Sempera, 200 mg per day) over 6 weeks was initiated. Five months later the patient's condition deteriorated again, with vomiting, nausea and pain behind the right eye plus increasing exophthalmus. Antifungal therapy was started again with amphotericin B and 5-fluorocytosine. Neutropenia did not occur. The patient became somnolent and deteriorated, a meningitis was suggested. Aspergillus antigen (titre 1:2, Pastorex) was detected in liquor. Anti-Aspergillus antibodies were not detectable. Both the right eye and retrobulbar fungal masses were eradicated by means of an exenteratio bulbi et orbitae. However, renal insufficiency and an apallic syndrome developed and the patient died. At autopsy, a mycotic aneurysm of the arteria carotis interna dextra was detected. The mycotic vasculitis of this aneurysm had caused a rupture of the blood vessel followed by a massive subarachnoidal haemorrhage. In addition, severe mycotic sphenoidal sinusitis and aspergillosis of the right orbit were seen, which had led to a bifrontal meningitis.
Mycoses 2001 Nov
PMID:Case report. Mycotic arteritis due to Aspergillus fumigatus in a diabetic with retrobulbar aspergillosis and mycotic meningitis. 1176 8

Although griseofulvin is considered the standard treatment of tinea capitis in children, alternatives are being investigated. Our purpose was to determine the efficacy of itraconazole for kerion and noninflammatory tinea capitis. An open label study was performed on five patients. It was planned to treat them with itraconazole until they were mycologically and clinically cured. A 28-112-day course of 100 mg itraconazole daily, combined with a topical antifungal treatment resulted in clinical and mycological cure in all children. One child stopped taking itraconazole after 28 days, before it was clinically cured, because of nausea. Nevertheless, this child also achieved clinical and mycological cure. No other side-effects were reported. In long-term follow-up evaluation of between 2 and 3.5 years no recurrence or reinfection was observed. There was complete regrowth of hair, even after kerion. These findings and the review of the literature suggest that itraconazole offers an alternative to griseofulvin for the treatment of tinea capitis in children, although it is more expensive and not approved by German state authorities for this indication.
Mycoses 2002 Feb
PMID:Itraconazole in the treatment of tinea capitis in children. Case reports with long-term follow-up evaluation. Review of the literature. 1185 29

A promising approach to improving outcomes in patients with cryptococcal meningitis is to use adjunctive passive immunotherapy with a monoclonal antibody (MAb) directed against the capsular polysaccharide of Cryptococcus neoformans. This is the first application of MAb therapy for the treatment of a fungal disease in humans. We determined the safety and maximum tolerated dose of the murine anticryptococcal MAb 18B7 in a phase I dose-escalation study. The subjects were human immunodeficiency virus-infected patients who had been successfully treated for cryptococcal meningitis. Six dosing cohorts received MAb 18B7 at 0.01 to 2 mg/kg of body weight as a single infusion. Three patients each received 0.01, 0.05, 0.2, and 0.5 mg of MAb 18B7 per kg without significant adverse events. Four of the subjects who received the 1-mg/kg dose had mild study drug-associated toxicity, including transient nausea, vomiting, back pain, and urticarial rash. Two of the subjects who received 2 mg/kg developed drug-associated mild to moderate nausea, vomiting, chills, and myalgias. One of the subjects who received 2 mg/kg developed intracranial hypertension 10 weeks after MAb 18B7 administration. Serum cryptococcal antigen titers in the cohorts receiving doses of 1 and 2 mg/kg declined by a median of twofold at 1 week and a median of threefold at 2 weeks postinfusion, but the titers subsequently returned toward the baseline values by week 12. The half-life of MAb 18B7 in serum was approximately 53 h, while the MAb was undetectable in the cerebrospinal fluid of all patients. These data support the continued investigation of MAb 18B7 at a maximum single dose of 1.0 mg/kg.
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PMID:Phase I evaluation of the safety and pharmacokinetics of murine-derived anticryptococcal antibody 18B7 in subjects with treated cryptococcal meningitis. 1572 88

Fever is the principle sign of infection in neutropenic patient and frequently may be the only evidence of infection. The pattern of fever in neutropenia is non-specific and not pathognomonic of any type of infections or non-infectious process and can be suppressed by the antipyretic effects of drugs such as corticosteroids. Neutropenia, resulting from cytotoxic chemotherapy is the most common risk factor for severe infections in hematological malignancies. The duration of neutropenia also contributes significantly to the risk of serious infections. This risk is significantly greater a lower neutrophil counts, such that 100% patients with ANC <100 cells/microl lasting 3 weeks or more develop documented infections. The prompt initiation of empirical antibiotics in febrile neutropenia has been the most important advance in the management of the immunocompromised host. The initial empirical antibiotic regimen started at presentation of the febrile episode frequently requires modifications especially in high-risk febrile neutropenia. Neutropenic patients who remain febrile despite 4-7 days of broad spectrum antibacterial therapy are at a high risk of invasive fungal infection. Empirical antifungal therapy with Amphotericin B in persistently febrile neutropenic patients and other high risk patients has shown to reduce the risk of invasive fungal infection by 50-80% and the risk of fungal infection related mortality by 23-45% in 1980's. The IDSA has recommended that amphotericin B at 0.5-0.7 mg/kg/day be administered till marrow recovery. This approach is limited however by the adverse effects caused by drug infusion (fever, chills, myalgias, nausea, hypotension and bronchospasm). Lipid formulations which improve the therapeutic ratio of the traditional formulation are available. The safety and efficacy of these formulations is well established. These formulations have comparable efficacy and are less nephrotoxic than conventional amphotericin B.A lipid formulation of amphotericin B is appropriate as initial empirical therapy or as definitive therapy for proven mycosis in high risk patients receiving concomitant nephrotoxic drugs (cyclosporine), those with pre-existing renal impairment and those with protracted neutropenia during which dose limiting toxicity may occur.
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PMID:Febrile neutropenia in haematological malignancies. 1651 55


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