Comparison of Tobramycin, Gentamicin, Colistin, and Carbenicillin in Pseudomonas Sepsis in Monkeys

Intravenous inoculation of 3.4 x 10(10) to 7.4 x 10(10)Pseudomonas aeruginosa organisms into rhesus monkeys 4 days after intravenous or intratracheal inoculation of 2.0 to 2.5 mg of vincristine sulfate resulted in fatal sepsis in eight of nine monkeys. After intramuscular administration, in two equal doses, of 5 mg of tobramycin, gentamicin, and colistin per kg per day beginning 16 hr after challenge, 4 of 11, 4 of 11, and 3 of 10 monkeys died, respectively. Administration of daily doses of 100 to 400 mg of carbenicillin per kg was followed by death in 5 of 12. Duration of illness in the surviving monkeys in each therapy group was similar. Under the conditions of this study, prior administration of vincristine sulfate resulted in a decrease in leukocytes and enhanced susceptibility to Pseudomonas infection. Using this model for studies of comparative efficacy of antibiotics, we observed comparable results after treatment with tobramycin, gentamicin, colistin, and carbenicillin.     

Sonography of abdominal posttransplant lymphoma

Five patients developed abdominal lymphoma an average of 89 months after successful renal transplantation. Sonographically, the lymphomas presented as bulky intraperitoneal masses or focal deposits in the liver. These lesions exhibited good sound transmission and intrinsic patterns ranging from sparse, soft echoes to coarse trabeculations. Prompt diagnosis of this serious late complication of renal transplantation is crucial.     

Religion, spirituality, and medicine: research findings and implications for clinical practice

A growing body of scientific research suggests connections between religion, spirituality, and both mental and physical health. The findings are particularly strong in patients with severe or chronic illnesses who are having stressful psychologic and social changes, as well as existential struggles related to meaning and purpose. Recent studies indicate that religious beliefs influence medical decisions, such as the use of chemotherapy and other life-saving treatments, and at times may conflict with medical care. This article addresses the ways physicians can use such information. Spirituality is an area that makes many physicians uncomfortable, since training in medical schools and continuing medical education programs are limited. Not only do most physicians lack the necessary training, they worry about spending additional time with patients and overstepping ethical boundaries. While these concerns are valid, each can be addressed in a sensible way. Taking a spiritual history, supporting the patient's beliefs, and orchestrating the fulfillment of spiritual needs are among the topics this article will address. The goal is to help physicians provide medical care that is sensitive to the way many patients understand and cope with medical illness.     

The effect of flatfoot deformity and tendon loading on the work of friction measured in the posterior tibial tendon

BACKGROUND: There is limited information regarding the mechanical factors contributing to the progression of posterior tibial tendon dysfunction. Therefore, an investigation of the mechanical forces on the posterior tibial tendon may improve our understanding of this pathology. METHODS: The gliding resistance and excursion of the posterior tibial tendon in the retromalleolar region was measured in seven cadaveric lower limbs in the coronal, transverse, and sagittal planes. These data were used to calculate the work of friction and to characterize the effect of different tendon loading levels (0.5, 1.0, and 2.0 kg) in the intact and flatfoot conditions. FINDINGS: Flatfoot deformity significantly increased the excursion of the posterior tibial tendon (P<0.05), increased forefoot and hindfoot range of motion in the coronal and transverse planes (P<0.05) and the work of friction in the coronal and transverse planes (P<0.05), but not in the sagittal plane. There was a significant increase in the work of friction between 0.5 and 2 kg (P<0.05) in all three planes of motion. INTERPRETATION: The motions in the coronal and transverse planes have a greater effect on the work of friction of the posterior tibial tendon than sagittal plane motion in the flatfoot condition. This study suggests that aggressive treatment of early stage PTT dysfunction with bracing designed to limit coronal and transverse motions, while permitting sagittal motion should be investigated further. Such bracing may decrease the potential of progressive deformity while allowing for more normal ambulation.     

Efficacy,pharmacokinetic, and safety assessment of adalimumab,a fully human anti-tumor necrosis factor-alpha monoclonal antibody,in adults with rheumatoid arthritis receiving concomitant methotrexate: a pilot study

BACKGROUND: Because traditional therapies for rheumatoid arthritis (RA) such as methotrexate (MTX) do not produce an adequate response in many patients, newer therapies that block the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) are increasingly being used in combination with MTX. OBJECTIVE: This study evaluated the efficacy, pharmacokinetics, and safety profile of adalimumab, a fully human anti-TNF alpha monoclonal antibody, when added to continuing MTX therapy. METHODS: This Phase I, randomized, dose-titration study consisted of a 4-week, double-blind, placebo-controlled treatment phase and a 26-month, open-label continuation phase. Patients with RA who had been taking stable doses of MTX (mean dose, 17 mg/wk) for > or =3 months before enrollment with an inadequate response were randomly assigned to receive 2 single doses of either adalimumab 0.25, 0.5, 1, 3, or 5 mg/kg i.v. or placebo in the double-blind phase. In the open-label phase, patients received treatment with 1 of the doses of adalimumab every other week or monthly for 18 months; patients were then switched to adalimumab 40 mg i.v. or SC every other week or monthly. The main efficacy end point was 20% improvement in American College of Rheumatology response criteria (ACR20). Other efficacy end points included 50% (ACR50) and 70% improvements in ACR response criteria. Pharmacokinetic parameters were analyzed for adalimumab and MTX during both phases of the study. Serum adalimumab concentrations were analyzed using a validated enzyme-linked immunosorbent assay relying on the double-antigen principle. Peak and trough concentrations were determined from observed concentration-time data, and a modeling approach was used to estimate total serum clearance, mean apparent terminal half-life, apparent volume of distribution at steady state, and area under the concentration-time curve. RESULTS: Sixty patients entered the double-blind phase, 45 receiving adalimumab and 15 receiving placebo; 1 placebo recipient chose not to continue into the open-label phase. Overall, the study population included 47 (78.3%) women and 13 (21.7%) men. The mean age was 52.9 years (range, 24-73 years), and the mean body weight was 69.7 kg (range, 43-98 kg). ACR20 and ACR50 responses were achieved on at least 1 assessment during the 4-week double-blind phase by a respective 29 (64.4%) and 11 (24.4%) of 45 patients receiving active treatment and by 4 (26.7%) and none of the 15 patients receiving placebo. Responses to adalimumab were rapid, with 10 (22.2%) of 45 patients achieving an ACR20 response within 24 hours of dosing. Of 29 adalimumab recipients who had an ACR20 response, 18 (62.1%) had a duration of response (time from first occurrence of a response to first occurrence of a nonresponse) of 1 to 2 weeks, and 11 (37.9%) had a duration of response of 3 to 13 weeks. The pharmacokinetic properties of adalimumab appeared to be linear. The mean apparent terminal half-life after a single intravenous dose of adalimumab ranged from 15 to 19 days in the 5 dose groups. Repeated administration of adalimumab had no statistically significant effect on the pharmacokinetics of MTX, indicating that dose adjustment of MTX is not necessary. Adalimumab was well tolerated, and there were no dose-related adverse events. CONCLUSIONS: Among patients with active RA who had not had an adequate response to MTX, addition of adalimumab to MTX achieved statistically significant, long-term improvement compared with placebo plus MTX (P < or = 0.05), as indicated by ACR responses at 26 months. The combination was well tolerated. Adalimumab exhibited linear pharmacokinetics. In this selected patient population, adalimumab's long half-life of 15 to 19 days supports every-other-week dosing. Coadministration of adalimumab did not alter serum levels of MTX.     

Innominate artery compression of the trachea: an unusual cause of apnea in a 12-year-old boy

Innominate artery compression of the trachea is a common cause of airway obstruction in infants and young children. The clinical significance of this lesion, even when compression is documented endoscopically or radiographically, is controversial. Obstructive respiratory symptoms occur in only a fraction of such cases, and symptomatic patients are most commonly detected in the first year of life. We present a case of a 12-year-old boy with a chief complaint of progressive stridor and apnea who was diagnosed with symptomatic innominate artery compression of the trachea. We reviewed the literature regarding the pathology, diagnosis, and treatment of this condition.     

这项临床试验完成注册了吗?--国际医学杂志编辑委员会声明

2004年9月,国际医学杂志编辑委员会(ICMJE)成员联合发表述评,旨在推动所有临床试验进行注册[1]。我们声明,只有当某项试验在征集首位患者之前就进行了注册,才会考虑发表其研究结果。该政策适用于在2005年7月1日及以后开始征募患者的试验。由于许多目前正在进行中的试验开始时都没有注册,对于这些试验我们将注册截止时间延长到2005年9月13日以前。我们当前和今后的目标是推动建立一个全面的、公众可及的临床试验数据库。对于那些承受风险参与临床试验的众多志愿者来说,完全注册是一种恰当的回报方式。他们有权知道通过他们的无私奉献换来的…     

Inherited IFNAR1 Deficiency in a Child with Both Critical COVID-19 Pneumonia and Multisystem Inflammatory Syndrome

Journal of Clinical Immunology - Inborn errors of immunity (IEI) and autoantibodies to type I interferons (IFNs) underlie critical COVID-19 pneumonia in at least 15% of the patients, while the...