Protocol-directed weaning: a process of continuous performance improvement

The use of a nursing-directed and/or respiratory therapist-directed protocol in many intensive care units for weaning from mechanical ventilation is associated with a shorter duration of ventilation and length of stay in the ICU. Most protocols have two formal components: the daily screening of a set of simple observations or interventions to identify readiness to proceed, followed by a spontaneous breathing trial that tests the patient's ability to breathe independently. The daily screen is designed to identify potential barriers regarding medical stability, level of consciousness, oxygenation, ventilation, and airway patency and protection. However, one must avoid selecting criteria that are too restrictive, potentially delaying the discontinuation of ventilation.     

Nonsteroidal anti-inflammatory drugs and gastroduodenal injury

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a commonly prescribed and over-the-counter class of drugs in the United States, with widespread use for various indications. The increased risk of gastrointestinal toxicity with the use of nonsteroidal medications has been well recognized. Pathogenesis of nonsteroidal toxicity is direct as well as systemic, secondary to prostaglandin inhibition. There are several risk factors to identify patients at a high risk for nonsteroidal toxicity. NSAID-related ulcer complications can be reduced by prophylaxis with prostaglandin analog drugs such as misoprostol or high-dosage proton-pump inhibition.     

Single variable domain antibody as a versatile building block for the construction of IgG-like bispecific antibodies

Bispecific antibodies (BsAb) have been traditionally utilized to redirect cytotoxic effector cells and agents to kill tumor cells expressing the target antigens. Recently a new concept is emerging to develop BsAb that simultaneously block the functions of two tumor-associated targets, eg., growth factor receptors, for enhanced antitumor efficacies. Broad clinical applications of BsAb have been, and still are, significantly hampered by the difficulty in producing the materials in sufficient quantity and quality by traditional approaches. Here we describe a recombinant approach for the production of an Fc domain-containing, IgG-like tetravalent BsAb, using a single variable domain (sVD) antibody as a versatile building block. In this method, a sVD of a defined specificity is genetically fused to either the N-terminus of the light chain or the C-terminus of the heavy chain of a functional IgG antibody of a different specificity. A model BsAb was constructed using a sVD to mouse platelet derived growth factor receptor alpha and a conventional IgG antibody to mouse platelet derived growth factor receptor beta. The BsAb were expressed in mammalian cells and purified to homogeneity by a one-step Protein A affinity chromatography. Further, the BsAb retained the antigen binding specificity and the receptor neutralizing activity of both of its parent antibodies. Importantly, the BsAb inhibited the activation of both its target receptors in tumor cells stimulated by both platelet derived growth factor AA and BB, whereas the parent monospecific antibody only inhibited the activation of a single receptor stimulated by its cognate ligand. This format of BsAb should be readily applicable to the production of other BsAb recognizing any pairs of antigens.     

Brugada pattern electrocardiogram associated with supratherapeutic phenytoin levels and the risk of sudden death

The emergence of Brugada pattern on electrocardiogram in response to class IA or IC antiarrhythmic agents is widely utilized to diagnose concealed Brugada syndrome and recognized as a risk factor for sudden death. Phenytoin, a class IB antiarrhythmic agent, has not been reported to induce Brugada pattern. We report a patient who presented with Brugada electrocardiogram at supratherapeutic phenytoin level. Considering that patients with syncope may falsely be labeled to have seizures and some epilepsy patients are at increased risk of sudden death, all patients with supratherapeutic phenytoin level should be evaluated with an electrocardiogram for emergence of Brugada pattern.     

Evaluation of Shoulder Disorders by 2-[F-18]-fluoro-2-deoxy-D-glucose Positron Emission Tomography and Computed Tomography

Background

Although flourine-18-flourodeoxyglucose (FDG) positron emission tomography (PET) has a limitation for localizing anatomical structures, combining it with computed tomography (CT) has made it more efficient for overcoming such limitations. This study aims to evaluate the efficacy of PET/CT for evaluating diseases of the shoulder.

Methods

Retrospective examination was performed on 25 patients who underwent FDG-PET/CT scanning. All the patients were over 60 years of age, and they were evaluated both clinically and radiologically for shoulder pain. The study period was from May, 2006 to May, 2008. One of the patients had metastatic lesion in a shoulder and this patient was excluded from the study, so the total number of subjects in the study was finally 24 patients.

Results

PET/CT showed 67% sensitivity, 73% specificity, a positive predictive value of 60%, a negative predictive value of 79%, 27% false positivity and 33% false negativity concerning shoulder pain. PET/CT showed negative finding in 4 cases that were successfully treated by operative treatment (rotator cuff tear [RCT], 3 cases; impingement syndrome, 1 case). Negative findings were also noted in 6 cases in which the pain subsided after conservative treatment (RCT, 1 case; suspected RCT, 2 cases; impingement syndrome, 3 cases). All the patients with osteoarthritis and rheumatoid arthritis had positive findings on PET/CT scanning.

Conclusions

PET/CT is a useful adjunct to the existing imaging modalities to assess functional and pathophysiologic processes and at a very early stage, and so PET/CT can help physicians make better preoperative and postoperative decisions on treatment.     

Convenient synthesis of novel 4-substitutedamino-5-trifluoromethyl-2,7-disubstituted pyrido[2,3-d] pyrimidines and their antibacterial activity

Novel pyrido[2,3-d]pyrimidines 4 have been synthesised starting from 2-amino-4-trifluoromethyl-6-substituted nicotinonitriles 1 via imine formation, selective amination followed by Dimroth rearrangement. Compounds 4 were screened against Gram +ve and -ve bacteria in vitro. Compounds 4h and 4d showed significant activity against all species of Gram positive bacteria and moderate activity against Gram negative bacteria. N-2,4 difluorophenyl compounds 4l and 4m were the least active among all the compounds. All the compounds were inactive against Pseudomonas aeruginosa at the maximum concentration of 200 microg ml(-1).     

Delivery of Predialysis Care in an Academic Referral Nephrology Practice

The purpose of this study was to obtain a detailed picture of the delivery of all aspects of pre-end stage renal disease (ESRD) care in an academic nephrology practice. The study consisted of a cross-sectional review of the charts of 111 patients with chronic kidney disease (CKD) (Creatinine > 1.5 mg/dL for males, Creatinine > 1.3 mg/dL for females) followed either in a private practice or a public hospital clinic. Charts were reviewed for evidence of a number of quality of care items including the degree of blood pressure control, the use of angiotensin II blockade, treatment of anemia, bone disease, and cardiovascular risk factors, as well as evidence of dialysis orientation and vascular access placement. Compared with previous published studies, this study shows encouraging trends towards better outcomes in at least two areas with evidence of improvement in hemoglobin levels, use of angiotensin II blockade, and degree of blood pressure control. However it also reveals many areas where care could be improved. This was particularly true in the areas of access placement, bone and mineral metabolism, and cardiovascular disease. It will be interesting to see whether the recent introduction of CKD guidelines by the National Kidney Foundation (NKF) and the associated educational initiatives for primary care physicians and nephrologists that are planned will further serve to improve the management of CKD patients in the years to come.