Human islet mass,morphology, and survival after cryopreservation using the Edmonton protocol

The aim of this study was to assess recovery, cell death, and cell composition of post-thaw cultured human islets. Cryopreserved islets were provided by the Clinical Islet Transplant Program, Edmonton, Canada. Islets were processed using media prepared in accordance with Pre-Edmonton and Edmonton protocols. Cryopreserved islets were rapidly thawed and cultured for 24 h, 3 d, 5 d, and 7 d, following which they were processed for histology. Islet quantification, integrity, morphology and tissue turnover were studied via hematoxylin and eosin stained sections. Ultrastructure was studied by electron microscopy and endocrine cell composition by immunohistochemistry. Using the Pre-Edmonton protocol, islet recovery was 50.1% and islet survival was 50% at 24 h while for the Edmonton protocol, the islet recovery was 69.4% (p < 0.001) and islet survival, 50% at ≈2.5 d. With an increasing culture duration although the physical integrity was retained there was an increasing loss of cohesivity both at light microscopic and at ultrastructure level regardless of the protocols used. Percentage islet survival and tissue turnover correlated negatively with culture duration in both protocols. The Edmonton protocol appears to preserve the islets better. However, culture duration adversely affects islet survival and quality, indicating the need for more optimal cryopreservation and culture techniques.     

Interobserver agreement rate of the spontaneous breathing trial

Purpose

During the mechanical ventilation weaning process, the spontaneous breathing trial (SBT) is the confirmatory test of patients' capability to breathe unassisted. However, the SBT interobserver agreement rate (its reliability) is unknown, and our objective was to evaluate it.

Materials and Methods

This is a prospective, multicentric and observational study. Patients were included when the SBT criteria were fulfilled. Two physicians and 2 respiratory therapists (RTs) rated each SBT. The SBT interobserver agreement was measured using κ statistic and also the percentage of agreement with its 95% credible interval (CrI) calculated by a Bayesian inference.

Results

Ninety-three distinct physicians and 91 distinct RTs rated 130 SBTs. The κ coefficient was 0.46 for physicians and 0.57 for RT, indicating a moderate interobserver agreement rate. The percentage of agreement was 87.7% between physicians (95% CrI, 81.0%-92.3%) and 86.2% between RT (95% CrI, 79.2%-91.1%). The physicians' and RT' percentage of agreement were not statistically different (P = .71).

Conclusions

The SBT interobserver agreement rate is only moderate for physicians and RT. The percentage of agreement between 2 different SBT observers is 79.2% to 92.3%. Therefore, a relevant percentage of patients will have different extubation decisions depending on the SBT observer.     

The Opportunity Loss of Boarding Admitted Patients in the Emergency Department

Objectives: Boarding admitted patients in emergency department (ED) treatment beds has been recognized as a major cause of ED crowding and ambulance diversions. When process delays impede the transfer of admitted patients from the ED to inpatient units, the department's capacity to accept new arrivals and to generate revenue from additional patient services is restricted. The objective of this study was to determine the amount of functional ED treatment capacity that was used to board inpatients during 12 months of operations at a community hospital and to estimate the value of that lost treatment capacity.
Methods: Historical data from 62,588 patient visits to the ED of a 450-bed nonprofit community teaching hospital in south central Pennsylvania between July 2004 and June 2005 were used to determine the amount of treatment bed occupancy lost to inpatient holding and the revenue potential of utilizing that blocked production capacity for additional patient visits.
Results: Transferring admitted patients from the ED to an inpatient unit within 120 minutes would have increased the functional treatment capacity of the ED by 10,397 hours during the 12 months of this study. By reducing admission process delays, the hospital could potentially have accommodated another 3,175 patient encounters in its existing treatment spaces. Providing emergency services to new patients in ED beds formerly used to board inpatients could have generated $3,960,264 in additional net revenue for the hospital.
Conclusions: Significantly higher operational revenues could be generated by reducing output delays that restrict optimal utilization of existing ED treatment capacity.     

Neonatal treatment with 192 IgG-saporin produces long-term forebrain cholinergic deficits and reduces dendritic branching and spine density of neocortical pyramidal neurons

The role of basal forebrain-derived cholinergic afferents in the development of neocortex was studied in postnatal rats. Newborn rat pups received intraventricular injections of 192 IgG-saporin. Following survival periods ranging from 2 days to 6 months, the brains were processed to document the cholinergic lesion and to examine morphological consequences. Immunocytochemistry for choline acetyltransferase (ChAT) and in situ hybridization for ChAT mRNA demonstrate a loss of approximately 75% of the cholinergic neurons in the medial septum and nucleus of the diagonal band of Broca in the basal forebrain. In situ hybridization for glutamic acid decarboxylase mRNA reveals no loss of basal forebrain GABAergic neurons. Acetylcholinesterase histochemistry demonstrates a marked reduction of the cholinergic axons in neocortex. Cholinergic axons are reduced throughout the cortical layers; this reduction is more marked in medial than in lateral cortical areas. The thickness of neocortex is reduced by approximately 10%. Retrograde labeling of layer V cortico-collicular pyramidal cells reveals a reduction in cell body size and also a reduction in numbers of branches of apical dendrites. Spine densities on apical dendrites are reduced by approximately 20-25% in 192 IgG- saporin-treated cases; no change was detected in number of spines on basal dendrites. These results indicate a developmental or maintenance role for cholinergic afferents to cerebral cortical neurons.      

Pharmacodynamic Activity of Five Oral Cephalosporins Against Haemophilus influenzae

Study Objectives . To determine the time above minimum inhibitory concentration (T > MIC) and serum bactericidal activity of five oral cephalosporins against two strains of Haemophilus influenzae. Design . Randomized, crossover study. Setting . University-associated research center. Subjects . Ten healthy volunteers. Interventions . Each subject received a single dose of cefpodoxime 200 mg, cefuroxime 500 mg, cefaclor 500 mg, cefprozil 500 mg, or loracarbef 400 mg each week for 5 weeks. Blood for serum levels was obtained at time zero and 1, 2, 3, 4, 6, 8, and 12 hours after each dose. Measurements and Main Results . Cefopodoxime produced serum concentrations above the MIC for more than 90% of the time for both β-lactamase-negative and -positive strains of H. influenzae. Moreover, it had serum bactericidal activity for 12 hours against both isolates. Cefuroxime was the second most active cephalosporin, with serum concentrations above the MIC of both isolates for 60% of the time. Cefuroxime provided serum bactericidal activity for 12 hours against the β-lactamase-negative strain and 6 hours against the β-lactamase-positive strain of H. influenzae. Even though the T > MIC was less than 50% of the study period for the other cephalosporins, all but cefaclor provided serum bactericidal activity for 12 hours against the β-lactamase-negative isolate. Cefaclor provided measurable serum bactericidal activity for only 3 hours. The duration of serum bactericidal activity of cefprozil, loracarbef, and cefaclor against the β-lactamase-positive isolate was 4, 2, and 0 hours, respectively. Conclusion . Cefpodoxime was the most active cephalosporin studied based on T > MIC and serum bactericidal activity against isolates of H. influenzae.