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56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thalidomide is approved in the United States for treating erythema nodosum leprosum, a complication of leprosy. The present study determined the single-dose oral pharmacokinetics and dose proportionality from 50 to 400 mg of Celgene's commercial Thalomid thalidomide formulation in an open-label, single-dose, three-way crossover study. Fifteen healthy subjects were given 50, 200, and 400 mg of thalidomide on three occasions, and blood samples were collected over 48 hours. Pharmacokinetic parameters were determined using noncompartmental methods, and dose proportionality was assessed by linear regression of dose-normalized Cmax and AUC0-infinity. No serious or unexpected adverse events occurred. The most common adverse events were dizziness, somnolence, headache, and nausea. One patient was discontinued because of pharyngitis. There was a significant deviation from proportionality for Cmax with increases being less than proportional than changes in dose. AUC0-infinity increased proportionally with dose, suggesting that the overall amount of thalidomide absorbed, as well as its clearance, is independent of dose over the range used. V/F was found to increase with dose. This was most likely due to the terminal rate constant, which is used to calculate V/F, actually representing the absorption process rather than elimination (i.e., flip-flop phenomenon). The terminal rate constant (absorption rate constant) for the highest dose was 50% less than for the other two lower doses. The less than proportional increases in Cmax were most likely due to thalidomide's low aqueous solubility. Thalidomide shows reasonable dose proportionality with respect to AUC from 50 to 400 mg.
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PMID:Thalidomide dose proportionality assessment following single doses to healthy subjects. 1140 35

Cilostazol, a type III phosphodiesterase inhibitor, was approved in the United States in 1999 for the reduction of the symptoms of intermittent claudication. This article summarizes the safety data from 8 cilostazol phase 3 controlled clinical trials, involving 2,702 patients: 1,374 receiving cilostazol, 973 assigned to placebo, and 355 taking pentoxifylline. The trials ranged from 12 to 24 weeks in duration. There were a total of 475 patient-exposure years on cilostazol, 357 patient-exposure years on placebo, and 135 patient-exposure years on pentoxifylline. Headache, diarrhea, and other gastrointestinal complaints were seen more often in cilostazol-treated than placebo-treated patients; pharyngitis and nausea were more common in pentoxifylline-treated than placebo-treated patients. Headache requiring discontinuation occurred in 1.3% of patients taking cilostazol 50 mg bid and 3.7% of those receiving cilostazol 100 mg bid, compared with 0.3% of placebo-treated patients. Discontinuations due to diarrhea, palpitations, or myocardial infarction were similar in cilostazol-, placebo-, and pentoxifylline-treated patients. The rate of serious cardiovascular events was similar in all 3 treatment groups. Myocardial infarction occurred in 1.0% of cilostazol-treated, 0.8% of placebo-treated, and 1.1% of pentoxifylline-treated patients. The incidence of stroke was 0.5% in both cilostazol- and placebo-treated patients and 1.1% in pentoxifylline-treated patients. Total cardiovascular morbidity and all-cause mortality was 6.5% for cilostazol 100 mg bid, 6.3% for cilostazol 50 mg bid, and 7.7% for placebo. There were 16 deaths occurring in 0.6%, 0.5%, and 0.6% of cilostazol-, placebo-, and pentoxifylline-treated patients, respectively. The evaluations showed no trend toward increased cardiovascular morbidity or mortality risk in patients receiving cilostazol. In addition, postmarketing surveillance in the United States, representing 70,430 patient-years of cilostazol exposure, has shown minimal accounts of myocardial infarction, stroke, or death. The safety profile of cilostazol in doses of 50 mg bid and 100 mg bid appears to offer an acceptable risk-benefit ratio in patients with intermittent claudication.
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PMID:Analysis of the cilostazol safety database. 1143 97

Crimean-Congo hemorrhagic fever was for the first time recognized in Yugoslavia in 1971. In this paper were presented clinical and laboratory findings of a patient infected with Crimean-Congo hemorrhagic fever in Kosovo in 1999. The disease was manifested with fever, headache, vomiting, myalgia, abdominal pain, pharyngitis, conjuctival injection, diarrhoea, hypotension, gingival bleeding, skin hemorrhages, hematuria, hepatomegaly, splenomegaly, jaundice, thrombocytopenia, prolonged prothrombin and partial thromboplastin time, high serum fibrinogen degradation product, leukocytosis, mild anemia, elevated levels of bilirubin and serum aminotransferases. Diagnosis was set clinically, epidemiologically and supported by serological tests. Supportive management of hypotension, multi-organ failure, coagulation disturbances the patient was of the utmost in the treatment together with the isolation and prophylactic measures.
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PMID:[Crimean-Congo hemorrhagic fever]. 1152 72

Primary HIV can be asymptomatic or result in a severe symptomatic illness. Common symptoms are pyrexia, pharyngitis, malaise, lethargy, maculopapular rash, mucous membrane ulceration, lymphadenopathy and headache. It can be reliably diagnosed by a positive virologic test in the absence of HIV-specific antibodies. Progression to late-stage disease is influenced by the severity of the symptoms in primary HIV infection, the duration of the illness, the presence of neurological symptoms and the presence of oral candidiasis. This stage is characterized by a very high viral load and infectiousness. Currently the experimental data are insufficient to recommend whether or not those diagnosed with primary HIV infection should routinely receive antiretroviral therapy.
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PMID:Primary HIV infection. 1183 60

Cefditoren pivoxil, an oral third-generation cephalosporin, was approved by the Food and Drug Administration in September 2001. It has been used in Japan for several years. The greatest therapeutic potential of cefditoren appears to be its activity against gram-positive and gram-negative organisms causing respiratory tract infections and skin and skin-structure infections, such as Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. Cefditoren is also effective against methicillin-susceptible strains of Staphylococcus aureus. Nevertheless, cefditoren has no activity against atypical pathogens, including Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella sp. Moreover, cefditoren does not inhibit Pseudomonas aeruginosa or Bacteroides fragilis. In virtually all studies, cefditoren has compared favorably against other orally administered antibiotics used against the most commonly isolated respiratory tract pathogens. Its side effect profile includes diarrhea, nausea, vomiting, headache, and dyspepsia. Cefditoren is indicated for treatment of mild-to-moderate acute exacerbations of chronic bronchitis, pharyngitis-tonsillitis, and uncomplicated skin and skin-structure infections caused by susceptible strains of organisms in adults and adolescents (> or = 12 yrs of age). Based on its reported antimicrobial activity, cefditoren has potential for empiric management of most commonly encountered respiratory tract infections. Additional studies will further define its role in clinical practice.
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PMID:Cefditoren, a new aminothiazolyl cephalosporin. 1238 78

Identifying children with acute pharyngitis caused by group A beta-hemolytic Streptococcus (GABHS) is an important task for pediatricians. This study examined the value of certain clinical symptoms and signs in predicting a positive culture result. A total of 442 children who presented at the outpatient department with pharyngeal erythema were enrolled. The clinical features of patients with positive throat cultures for GABHS were compared to those with negative culture results. Throat cultures were positive for GABHS in 120 (27%) patients. Patients aged between 5 and 10 years had a higher prevalence of GABHS pharyngitis. Significant differences between the groups with and without GABHS pharyngitis were noted for the presence of sore throat (p < 0.001), tonsillar swelling (p < 0.001), anterior cervical adenopathy (p = 0.004), and scarlatiniform rash (p < 0.001), but not for the presence of fever, cough, rhinorrhea, abdominal pain, headache, tonsillar exudate, or palatal petechiae. Despite these strong associations, none of these symptoms or signs had both high sensitivity and specificity, and the positive predictive values of these individual findings were never greater than 50%. The results indicate that diagnosis based on clinical grounds alone is unreliable although there are certain individual symptoms and signs that are associated with GABHS pharyngitis. These symptoms and signs may be helpful in modifying estimates of probability of infection with GABHS. Throat cultures in suspected patients remain mandatory.
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PMID:Predictive value of clinical features in differentiating group A beta-hemolytic streptococcal pharyngitis in children. 1274 28

Alefacept, human LFA-3/IgG1 fusion protein, is currently under clinical development for the treatment of chronic plaque psoriasis and other T cell mediated disorders. This recombinant protein binds CD2 on T cells and Fc gamma RIII on accessory cells (e.g., natural killer cells, macrophages), inhibiting T cell activation/proliferation and inducing selective T cell apoptosis. These effects are associated with selective reductions in memory-effector (CD4+ CD45RO+ and CD8+ CD45RO+) T cells. Two open-label studies were conducted in healthy male volunteers to evaluate the pharmacokinetics, biologic activity, and tolerability of a single dose of alefacept when administered as a 0.15 mg/kg 30-sec i.v. bolus (n = 12), 0.04 mg/kg intramuscular (i.m.) injection (n = 8), or 0.04 mg/kg 30-min intravenous (i.v.) infusion (n = 8). i.v. infusion produced a higher Cmax (0.96 +/- 0.26 mcg/ml vs. 0.36 +/- 0.19 mcg/ml) and a shorter Tmax (2.8 +/- 1.9 hr vs. 86 +/- 60 hr) when compared to i.m. injection. Based on AUC0-last and AUC0-infenity values, the relative bioavailability of i.m. to i.v. infusion was approximately 60%. After absorption from the i.m. injection was complete, the rate of alefacept elimination from the serum appeared consistent with the i.v. infusion half-life (approximately 12 days). Biologic activity was demonstrated by transient reductions in absolute number of CD2+ lymphocytes, with notable specificity for memory T-cell subsets. Alefacept was well tolerated; the most common adverse effects were headache, pharyngitis, rash, and myalgia. IM administration was not associated with significant local reactions. Results of these studies support i.v. bolus or i.m. administration of alefacept. An i.m. dose of approximately 150 to 200% of the i.v. dose is an appropriate and convenient alternative to i.v. administration.
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PMID:Pharmacokinetics, biologic activity, and tolerability of alefacept by intravenous and intramuscular administration. 1279 39

Cyclic neutropenia is an uncommon hematologic disorder characterized by a marked decrease in the number of neutrophils in the peripheral blood occurring at regular intervals. The neutropenic phase is characteristically associated with clinical symptoms such as recurrent fever, malaise, headaches, anorexia, pharyngitis, ulcers of the oral mucous membrane, and gingival inflammation. This case report describes a Japanese girl who has this disease and suffers from periodontitis and oral ulceration. Her case has been followed up for the past 5 years from age 7 to 12. The importance of regular oral hygiene, careful removal of subgingival plaque and calculus, and periodic and thorough professional mechanical tooth cleaning was emphasized to arrest the progress of periodontal breakdown. Local antibiotic application with minocycline ointment in periodontal pockets was beneficial as an ancillary treatment, especially during neutropenic periods.
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PMID:Oral manifestations of cyclic neutropenia in a Japanese child: case report with a 5-year follow-up. 1367 5

Acute human immunodeficiency virus (HIV) seroconversion illness is a difficult diagnosis to make because of its nonspecific and protean manifestations. We present such a case in an adolescent. A 15-year-old boy presented with a 5-day history of fever, sore throat, vomiting, and diarrhea. The patient also reported a nonproductive cough, coryza, and fatigue. The patient's only risk factor for HIV infection was a history of unprotected intercourse with 5 girls. Physical examination was significant for fever, exudative tonsillopharyngitis, shotty cervical lymphadenopathy, and palpable purpura on both feet. Laboratory studies demonstrated lymphopenia and mild thrombocytopenia. Hemoglobin, serum creatinine, and urinalysis were normal. The following day, the patient remained febrile. Physical examination revealed oral ulcerations, conjunctivitis, and erythematous papules on the thorax; the purpura was unchanged. Serologies for hepatitis B, syphilis, HIV, and Epstein-Barr virus were negative. Bacterial cultures of blood and stool and viral cultures of throat and conjunctiva showed no pathogens. Coagulation profile and liver enzymes were normal. Within 1 week, all symptoms had resolved. The platelet count normalized. Repeat HIV serology was positive, as was HIV DNA polymerase chain reaction. Subsequent HIV viral load was 350 000, and the CD4 lymphocyte count was 351/mm3. HIV is the seventh leading cause of death among people aged 15 to 24 in the United States, and up to half of all new infections occur in adolescents. Our patient presented with many of the typical signs and symptoms of acute HIV infection: fever, fatigue, rash, pharyngitis, lymphadenopathy, oral ulcers, emesis, and diarrhea. Other symptoms commonly reported include headache, myalgias, arthralgias, aseptic meningitis, peripheral neuropathy, thrush, weight loss, night sweats, and genital ulcers. Common seroconversion laboratory findings include leukopenia, thrombocytopenia, and elevated transaminases. The suspicion of acute HIV illness should prompt virologic and serologic analysis. Initial serology is usually negative. Diagnosis therefore depends on direct detection of the virus, by assay of viral load (HIV RNA), DNA polymerase chain reaction, or p24 antigen. Both false-positive and false-negative results for these tests have been reported, further complicating early diagnosis. Pediatricians should play an active role in identifying HIV-infected patients. Our case, the first report of acute HIV illness in an adolescent, emphasizes that clinicians should consider acute HIV seroconversion in the appropriate setting. Recognition of acute HIV syndrome is especially important for improving prognosis and limiting transmission. It is imperative that we maintain a high index of suspicion as primary care physicians for adolescents who present with a viral syndrome and appropriate risk factors.
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PMID:Acute human immunodeficiency virus syndrome in an adolescent. 1452 19

Primary human immunodeficiency virus type 1 (HIV-1) infection (acute retroviral syndrome) has been well characterized as a mononucleosis-like illness. Manifestations of HIV-1 infection such as pharyngitis, fever, morbilliform rash, myalgias, arthralgias, nausea, headache, emesis, and lymphadenopathy have been reported. Acute rhabdomyolysis has been reported as part of the acute retroviral syndrome on 11 different occasions. We report the case of a primary HIV-1 infection with acute rhabdomyolysis and review critically the other case reports.
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PMID:Primary human immunodeficiency virus type 1 infection in a patient with acute rhabdomyolysis. 1457 Mar 49


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