Biological mechanisms of the individual variability of the anxiolytic action of opioids

The opioid system is one in a number of peptidergic regulatory systems that support an appropriate anxiety level. The drugs that interact with the opioid system have been shown to influence anxiety, although there is a notable variability in their pharmacological effects. Biological mechanisms of this variability are considered to be the heterogeneity of opioid receptors, the ratio of the processes of their expression and desensitization, and the balance between the synthesis and degradation of endogenous opioid peptides. For instance, the anxiolythic effect of the synthetic derivate of enkephalin in rats was detected after stress-induced exhaustion of endogenous opioids, and its efficacy depended on the degree of delta- and mu-opioid receptor desensitization in some brain regions. The anxiolythic properties of the heptapeptide Selanc that has also been shown to affect the opioid system are most prominent in subjects with elevated activity of enzymes degrading endogenous opioid peptides. Thus, delicate correction of the opioid system with drugs of peptide nature is supposed to become a new approach to treatment of some forms of anxiety disorders accompanied with exhaustion of the endogenous opioid system and, in particular, of generalized anxiety disorder.     

Factors affecting unanticipated hospital admission following otolaryngologic day surgery

BACKGROUND: Day surgery constitutes an important part of modern otolaryngology practice. However, high rates of unplanned admissions remain an issue. OBJECTIVE: To determine the incidence, reasons, and predictive factors for unanticipated admission after ambulatory otolaryngologic surgery. METHODS: A retrospective review of all cases of unplanned admission following otolaryngology day surgery at a tertiary care centre over a 4-year period from 2000 to 2004. Data relating to patient demographics, physical status, surgical procedure, perioperative complications, and reasons for hospital admission were recorded. A case-control analysis of these parameters with nonadmitted day surgery patients was used for comparison. RESULTS: During the above period, 1106 patients underwent otolaryngologic day surgery, of whom 74 (6.7%) required admission. Fifty-seven percent of the patients were male, and the average age was 48.9 years. The three most common procedures with unplanned admission were open neck biopsy (27%), functional endoscopic sinus surgery (20.3%), and panendoscopy (16.2%). The reasons for admission could be divided into airway monitoring (37.7%), postoperative bleeding (28.6%), the need for supportive or pain management (19.5%), anesthetic complication (5.2%), cardiovascular complication (3.9%), clerical error (3.9%), and suspicion of a cerebrospinal fluid leak (1.3%). Risk factors for admission were determined to be an American Society of Anesthesiologists' class of 3 or greater, open neck surgical procedures, and a length of surgery of 60 minutes or greater. Minor factors included the use of general anesthesia, male gender, advanced age, and living far from a hospital. CONCLUSIONS: This study suggests strategies to reduce the rate of unplanned admission by means of careful preoperative assessment and planning, patient selection, careful scheduling of higher-risk patients, and appropriate postoperative observation and management.     

Katrina, the tsunami, and point-of-care testing: optimizing rapid response diagnosis in disasters

We assessed how point-of-care testing (POCT), diagnostic testing at or near the site of patient care, can optimize diagnosis, triage, and patient monitoring during disasters. We surveyed 4 primary care units (PCUs) and 10 hospitals in provinces hit hardest by the tsunami in Thailand and 22 hospitals in Katrina-affected areas. We assessed POCT, critical care testing, critical values notification, demographics, and disaster responses. Limited availability and poor organization severely limited POCT use. The tsunami impacted 48 PCUs plus island and province hospitals, which lacked adequate diagnostic instruments. Sudden overload of critical victims and transportation failures caused excessive mortality. In New Orleans, LA, flooding hindered rescue teams that could have been POCT-equipped. US sea, land, and airborne rescue brought POCT instruments closer to flooded areas. Katrina demonstrated POCT value in disaster responses. We recommend handheld POCT, airborne critical care testing, and disaster-specific mobile medical units in small-world networks worldwide.     

Ictal spiking patterns recorded from temporal depth electrodes predict good outcome after anterior temporal lobectomy

PURPOSE: Investigators have shown that the presence of ictal spiking (IS) recorded from temporal depth electrodes is associated with mesial temporal sclerosis (MTS). We investigated the relation of IS to seizure control and pathology after anterior temporal lobectomy (ATL). METHODS: All patients undergoing intracranial ictal monitoring from a single institution since 1989 were identified. Those who did not undergo ATL or had postoperative follow-up of <1 year were excluded. All received at a minimum bilateral temporal depth electrodes. Ictal recordings were reviewed for the presence of IS, and the proportion of seizures with IS was determined for each patient. Outcome was determined by using Engel's classification. Surgical specimens were reviewed for pathology. Statistics used were chi2, Fisher exact test, and Wilcoxon rank sum. RESULTS: Forty patients with 571 seizures were reviewed. In 292 seizures from 32 patients, IS was seen. Outcomes were 24 class I (22 with IS), five class II (four with IS), three class III (one with IS), seven class IV (four with IS), and one lost to follow-up (with IS). Pathologic review revealed 25 with MTS, 22 of whom had IS. The presence of IS was associated with class I outcomes (p = 0.04), but not MTS (p = 0.06). Patients with class I outcomes had a significantly greater proportion of seizures with IS (mean, 0.58 +/- 0.3) compared with other outcomes (mean, 0.30 +/- 0.3, p = 0.02). CONCLUSIONS: The presence of IS and higher proportion of seizures with IS correlated with good seizure outcome after ATL. This information may be used in preoperative counseling.     

Multicenter study of whole-blood creatinine, total carbon dioxide content, and chemistry profiling for laboratory and point-of-care testing in critical care in the United States

OBJECTIVES: To introduce a creatinine biosensor and a total carbon dioxide content (TCO2) method for whole-blood measurements, to evaluate the clinical performance of a new transportable analyzer that simultaneously performs these two and six other tests (Na+, K+, Cl-, glucose, urea nitrogen, and hematocrit), and to assess the potential of the new analyzer for point-of-care testing in critical care by comparing results obtained by nonlaboratory personnel and by medical technologists. DESIGN: Multicenter sites compared whole-blood measurements with the transportable analyzer to plasma measurements from the same specimens with local reference instruments. One site compared whole-blood results produced by nonlaboratory personnel vs. medical technologists and evaluated day-to-day and within-day precision at the point of care. SETTINGS AND PATIENTS: Four medical centers in the United States. Venous and arterial specimens from 710 critically ill patients with a variety of diagnoses. Point-of-care testing in the emergency room and operating room. RESULTS: The linear regression analyses at the four medical centers showed the following: creatinine (a) slope, 0.91 to 1.22, (b) y intercept, -0.07 to 0.15 mg/dL, and (c) r2, 0.77 to 1.00; and TCO2: (a) slope, 0.64 to 1.00, (b) y intercept, 1.36 to 9.6 mmol/L, and (c) r2, 0.52 to 0.72 (yi, whole-blood analyses; xi, plasma reference measurements). Bland-Altman plots also were used to assess multicenter creatinine and TCO2 results. Of the other analytes, K+, glucose, and urea nitrogen had the highest r2-values. For the eight chemistry profile tests performed at the point of care (yi, nonlaboratory personnel results; xi, medical technologist results), the average value of r2 was 0.96 (SD 0.08) in the operating room and 0.96 (SD 0.06) in the emergency room, and mean paired differences (yi - xi) were not statistically or clinically significant. Precision was acceptable. CONCLUSIONS: The performance of the creatinine biosensor and the TCO2 method was acceptable for whole-blood samples. Comparisons of whole-blood results from the transportable analyzer and plasma results from the local reference instruments revealed analyte biases that may be attributed to differences between direct whole-blood analyses and indirect-diluted plasma measurements and other factors. Performance of nonlaboratory personnel and medical technologists was equivalent for point-of-care testing in critical care settings. The whole-blood analyzer should be useful when patient care demands immediate results.     

Detection of natural anti-angiotensin converting enzyme antibodies in human serum using immunoenzyme technique

Solid-phase enzyme immunoassay (EIA) was developed for detecting natural antibodies to angiotensine-converting enzyme (ACE). Optimal conditions for detecting natural anti-ACE by EIA in the sera of donors and patients with disorders of arterial pressure are selected. The findings indicate that the level of natural anti-ACE is normally constant, while in the patients it is increased in 50% cases.     

Caffeine augments proteinuria in puromycin-aminonucleoside nephrotic rats

Several studies indicate that increased intrarenal adenosine concentrations may attenuate puromycin-aminonucleoside (PAN)-induced nephropathy in rats. The purpose of this study was to investigate the chronic effects of caffeine, a nonselective adenosine receptor antagonist, on renal function and structure in PAN-induced nephropathy. Animals were randomized to receive drinking water or 0.1% caffeine solution. PAN was administered in two doses to a subset from each group at 1 week (100 mg/kg, s.c.; Purom-1) and 15 wks (80 mg/kg, s.c.; Purom-2) after initiating caffeine treatment (PAN and CAFF-PAN groups). The remaining animals served as time controls (CON and CAFF groups). Renal excretory function was followed for 23 wks. Caffeine consumption significantly augmented PAN-induced proteinuria after both PAN injections (Purom-1 and Purom-2, p<0.05 and p<0.001 respectively; CAFF-PAN vs. PAN). In addition, caffeine potentiated the transient reduction in creatinine clearance (CrCl) induced by PAN. Caffeine consumption for 23 wks significantly reduced CrCl in conscious nephrotic animals (4.76 +/- 0.98 vs. 8.51 +/- 1.55 L/kg/day, CAFF-PAN vs. PAN). Seven days after both PAN injections, increased plasma renin activity was detected in animals that were consuming caffeine as compared with corresponding control groups (CAFF and CAFF + PAN vs CON and PAN, respectively). Eight weeks after the second injection of PAN, acute measures of renal hemodynamic and excretory function were compared in anesthetized animals and renal samples were analyzed for histological changes. In PAN-rats, caffeine treatment for 23 weeks significantly reduced inulin clearance (0.28 +/- 0.09 vs. 0.57 +/- 0.12 mL/min/gr kidney. CAFF-PAN vs PAN, p<0.05), tended to increase renal vascular resistance (59.0 +/- 9.5 vs. 42.9 +/- 5.5 mmHg/mL/min/gr kidney, CAFF-PAN vs. PAN, p < 0.06), potentiated the development of more severe tubulointerstitial damage (tubular atrophy, presence of proteinaceous material, tubular dilatation, interstitial inflammation, interstitial fibrosis), and tended to increase glomerulosclerosis. In conclusion, this study indicates that caffeine adversely affects renal function in PAN-nephrotic rats, and that this effect may be due, in part, to increased activity of the renin angiotensin system.