Antagonist efficacy in MORS196L mutant is affected by the interaction between transmembrane domains of the opioid receptor

In a previous study, we demonstrated that antagonists such as naloxone or naltrexone acted as full agonists at the mu-opioid receptor (MOR)/delta-opioid receptor (DOR) chimeric receptor (mudelta2, where the DOR sequence from the first extracellular loop to the carboxyl terminus was spliced to the MOR sequence) when a conserved serine residue in transmembrane 4 (TM4) was mutated to leucine. However, when Ser196 in the TM4 of MOR was mutated to Leu, antagonists exhibited partial agonistic properties. Since molecular modeling studies suggested transmembrane movement during receptor activation, the observed partial agonistic properties could be due to TM1 and TM7 interaction. Hence, MOR/DOR chimeric mutant receptors with the MOR TM1 and TM7 sequence (mudelta2mu7S196L) or with the MOR TM1 and TM6/7 sequence (mudelta2mu67S196L) were constructed to test such a hypothesis. Using four tests of opioid receptor activation, we found that the opioid antagonists were full agonists in chimeric mutant receptor if the TM1 and TM7 were from different opioid receptors. Additionally, when two of the TM7 amino acid residues of MORS196L receptor mutants were mutated (T327A and C330S), resulting in a mutant receptor with DOR TM7 sequence, opioid antagonist naloxone exhibited full agonistic properties. These data suggest that the efficacy of opioid antagonists in the Ser196 mutant can be affected by the interaction between TM1 and TM7.     

Exploring Empathy: A Conceptual Fit for Nursing Practice?

After three decades, the efficacy of empathy in the clinical setting remains undocumented. Recently, concerns have been raised that the concept may be inappropriate and even harmful to the nurse-patient relationship. An analysis of the concept indicates that empathy consists of moral, emotive, cognitive and behavioral components. By tracing the integration of this concept into nursing, we suggest that empathy was uncritically adopted from psychology and is actually a poor fit for the clinical reality of nursing practice. Other communication strategies presently devalued, such as sympathy, pity, consolation, compassion and commiseration, need to be reexamined and may be more appropriate than empathy during certain phases of the illness experience. Directions for future research are suggested.     

Eradication of non-typhoid salmonellae in acute enteritis after therapy with ofloxacin for 5 or 10 days

Eradication of non-typhoid salmonellae was evaluated in a randomized, double-blinded study of 49 patients with acute enteritis after therapy with ofloxacin 400 mg once daily for 5 or 10 days. Early eradication of salmonellae was found in 57% of patients in the 5 day therapy group and in 74% of patients in the 10 day therapy group. This difference was larger among severely ill patients. Together with our previous study of ofloxacin therapy for 3 days or placebo, this shows that early eradication of non-typhoid salmonellae increases with duration of ofloxacin therapy without an increase in persistence of salmonellae in stools or development of resistant strains.     

Assay of cefotaxime by high-pressure-liquid chromatography

A high-pressure-liquid chromatographic (HPLC) procedure for quantitative assay of cefotaxime (CT) and its major metabolite in serum of normal individuals, desacetyl cefotaxime (DACT), is described. It employs Lichrosorb RP-8, elution with phosphoric-acid-methanol and UV absorption at 310 nm. The method is optimized for cefotaxime and allows differentiation between the parent compound and the biotransformation product DACT. The lower assay sensitivity level of CT and DACT is 0.3 microgram/ml. Correlation between HPLC and microbiological assay with Escherichia coli or Proteus rettgeri of pooled serum with CT added is r = 0.99. The method is rapid; processing of one sample takes 17 min. Use of HPLC avoids the errors of microbiological assays which derived from the presence in patient sera of different ratios of CT and DACT. The apparent rate of serum elimination is linearly related to the sensitivity of the microbial assay indicator strain to DACT. There is synergistic antibacterial activity between CT and DACT regardless of relative minimum inhibitory concentrations of the agents.     

Impaired left ventricular filling is associated with decreased pulse oximetry values

Objectives. The aim of this study was to investigate the association between echocardiographic measures of diastolic left ventricular dysfunction and decreased arterial oxyhaemoglobin saturation measured with pulse oximetry (SpO₂). Design. This is a cross-sectional population-based survey of Norwegian adults. Values obtained using echocardiography, pulse oximetry, and spirometry were included. The primary outcome was abnormal mitral Doppler inflow, defined as normal: E/A ratio 0.75–1.5 and EDT?≥?140?ms; abnormal: E/A ratio?<0.75 or >1.5 or EDT?<140?ms. The associations between this outcome and possible predictors, including SpO₂?≤?95%, were analysed using univariable and multivariable logistic regression. Results. A total of 1782 participants aged 50 years or older (54% women, mean age 67.5 years) were included in the analysis. Abnormal mitral Doppler inflow was found in 595 participants. After adjusting for age, gender, previous myocardial infarction, smoking history, dyspnoea, obesity, and decreased lung function, SpO₂?≤?95% predicted abnormal mitral Doppler flow with an odds ratio (OR) of 1.6 [95% confidence interval (CI) 1.1–2.4]. Hypertension and BMI?>?=30 were also significant predictors of impaired filling, with OR of 1.7 (95% CI 1.1–2.7) OR and 1.5 (95% CI 1.2–1.9), respectively. Conclusion. Decreased SpO₂ was a significant predictor of abnormal mitral Doppler flow. Diastolic dysfunction should be considered when SpO₂?≤?95% is found.     

Angiotensin‐converting enzyme inhibition increases glucose‐induced insulin secretion in response to acute restraint

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Derivation and validation of a simple risk score for predicting 1-year mortality in stroke

Context Numerous models have been presented for the prognosis in acute stroke; however they have been criticized for being difficult to use, and few have been validated in independent samples. Objectives To develop simple risk score models for 1-year mortality in acute stroke in patients > 60 years old and validate the models. Design From a cohort of 2321 consecutive patients > 60 years of age with acute stroke in one hospital, we randomly selected 800 patients for chart review. Among 737 patients with validated acute stroke, we randomly split the sample into (1) a derivation (60%; n = 442) and (2) a validation sample (40%; n=295).We used logistic regression to develop three models with 2–4 covariates and a corresponding risk score from the derivation sample. The models were validated using area under the receiver operating curves. Results Three risk score models for 1-year mortality after stroke were developed using combinations of age, Canadian Neurological Scale score (CNSscore) (≤ 3.5 = 0, >3.5 = 1), Charlson comorbidity index and stroke type (ischemic = 0, hemorrhagic = 1). Both 2-variable (Age – 60 + (30*CNSscore)), 3-variable (Age – 60 + (30*CNSscore) + 4*Charlson)) and 4-variable (Age – 60 + (25*CNSscore) + (5*Charlson) + (18*Stroke type)) models reliably predicted the outcome with an area under the receiver operating curve ranging 0.71 to 0.72. Conclusions Simple models incorporating two to four covariates reliably predicted 1-year mortality. Such models can be used to stratify prognosis in clinical practice, research or intervention trials.     

Improvements in prostate brachytherapy dosimetry due to seed stranding

PURPOSE: Prostate brachytherapy with suture embedded seeds has emerged as a popular technique to reduce seed migration and to improve dosimetry. Various trials have shown improved dosimetry with seed fixity, whereas others have shown no benefit and possible detriment to suture embedded seeds. In order to contribute to the understanding of whether seed stranding improves dosimetry, we present retrospective data from our institution. METHODS AND MATERIALS: We analyzed 80 patients treated between April 29, 2001 and June 19, 2006, receiving I-125 monotherapy for prostate cancer. Brachytherapy patients at the University of California, Los Angeles (UCLA) were initially treated using a transperineal approach with loose seeds. Subsequent to October 26, 2002, all patients were implanted using suture embedded seeds. Dosimetric quantifiers were calculated based on a CT obtained 1-month postimplantation. RESULTS: Dosimetry of patients treated with stranded seeds showed significant improvement. Specifically, the V100 (volume of the prostate receiving 100% of the prescribed dose) improved from 88% to 92% (p<0.05), and the D90 (maximum dose received by 90% of the prostate) improved from 143 to 155 Gy (p<0.05). CONCLUSIONS: At UCLA, the use of suture embedded seeds resulted in a significant improvement in our dosimetric quantifiers. Based upon other published studies, this improvement in dosimetry may translate into improved patient outcomes.