An early example of evidence-based medicine: hypoxemia due to nitrous oxide

Diffusion anoxia. By Bernard Raymond Fink. Anesthesiology 1955; 16:511-14.In 1955, Dr. Bernard Raymond Fink published his findings that described the mechanism by which hypoxemia occurred when nitrous oxide-oxygen anesthesia was discontinued and room air breathing commenced. Using an ear oximeter and brachial artery blood gases, he measured oxygen saturation in eight healthy patients who had received 75% nitrous oxide-25% oxygen for gynecologic surgery. He showed that oxygen saturation decreased from 5% to 10% and often reached a value below 90% when the patient began room air breathing after the nitrous oxide-oxygen was discontinued. The effect was seen over a 10-min period. He concluded that "anoxia arises because the outward diffusion of nitrous oxide lowers the alveolar partial pressure of oxygen." This phenomenon can become a causative factor of cardiac arrest in patients with impaired pulmonary or cardiac reserves.     

Project back-on-track at 1 year: a delinquency treatment program for early-career juvenile offenders

OBJECTIVE: This study assessed the effectiveness of Project Back-on-Track, an after-school diversion program that uses a multimodal approach for the treatment of early-career juvenile offenders. METHOD: Project Back-on-Track completers (30 of 41 enrollees; 73%), aged 9 to 17 years, 63% female, participated in a 4-week cycle of treatment consisting of group and family therapies, parent groups, educational sessions, community service projects, and empathy-building exercises. These youths attended the program 2 hours per day, 4 days a week, allowing for 32 hours of contact with the program per cycle; parents attended the program for 15 hours per cycle. Most youths were referred for violent offenses and met criteria for conduct disorder. RESULTS: Project Back-on-Track completers were significantly less likely than matched controls to have committed subsequent criminal offenses at 12 months. In addition, they had significantly fewer subsequent criminal charges at 9- and 12-month follow-up intervals than the control group. By decreasing the frequency of criminal recidivism, it is estimated that Project Back-on-Track resulted in savings to society of approximately $1,800 per youth enrolled after 1 year. CONCLUSION: At 1-year follow-up, findings suggest that treatment through Project Back-on-Track was effective in reducing criminal recidivism and costs in a population of early-career juvenile offenders.     

Impact of patient characteristic factors on the dynamics of liver glucose metabolism: Evaluation of multiparametric imaging with dynamic whole-body 18F-fluorodeoxyglucose-positron emission tomography

Aims

To assess the impact of various patient characteristics on the dynamics of liver glucose metabolism using automated multiparametric imaging with whole-body dynamic ¹⁸F-fluorodeoxyglucose (FDG)-positron emission tomography (PET).

Materials and Methods

We retrospectively enrolled 540 patients who underwent whole-body dynamic FDG-PET. Three quantitative indices representing hepatic glucose metabolism [mean standardized uptake value normalized by lean body mass (SULmean), metabolic glucose rate (kinetic index) and distribution volume (DV)] were measured from multiparametric PET images produced automatically based on the Patlak plot model. Patient characteristics including age, sex, body mass index, fasting time, blood glucose level, and the presence of diabetes mellitus (DM) or hepatic steatosis (HS) were collected. We examined the correlations between the characteristic factors and three quantitative indices using multiple regression analysis.

Results

The success rate of kinetic analysis using multiparametric PET imaging was 93.3% (504/540). Hepatic SULmean was significantly correlated with age (p < .001), sex (p < .001) and blood glucose level (p = .002). DV was significantly correlated with age (p = .033), sex (p < .001), body mass index (p = .002), fasting time (p = .043) and the presence of HS (p = .002). The kinetic index was significantly correlated with age (p < .001) and sex (p = .004). In the comparison of the healthy, DM and HS groups, patients with DM had a significantly increased SULmean, whereas patients with HS had a significantly decreased DV.

Conclusions

Our results showed that liver glucose metabolism was influenced by various patient characteristic factors. Multiparametric FDG-PET imaging can be used to analyse the kinetics of liver glucose metabolism in routine clinical practice.     

Influence of coating strain on calcium phosphate thin-film dissolution.

The success of calcium phosphate (CaP) coatings used to accelerate initial bone growth onto dental implants can vary depending on the CaP phases present in the coating. In this study, the effect of CaP coating crystal structure and morphology on dissolution rates was investigated. RF magnetron-sputtered CaP coatings (NTC) were compared to a less strained coating (HTC) obtained from heat treatment of sputtered samples at 550 degrees C. Coating strain differences were apparent in XRD spectra where hydroxyapatite-like planes shifted by 0.5 degrees 2theta and 0.05 degrees 2theta for the NTC and HTC coatings, respectively. HTC XRD peak widths were broader than NTC peak widths, indicating smaller crystals or grain sizes. These differences in grain size were corroborated by imaging with scanning probe microscopy. NTC coatings dissolved at a 300% faster rate than HTC coatings. A major factor contributing to this kinetic effect was the level of strain in both coatings. These results suggest an alternate design for CaP coatings can be obtained through the manipulation of coating strain. Using this approach, delivery of different ionic gradients from CaP coatings to surrounding tissue environments can be obtained from surfaces having similar chemistries.     

Accuracy of Pathologic Techniques for the Diagnosis of Metastatic Melanoma in Sentinel Lymph Nodes

Background: Sentinel lymph node (SLN) biopsy can accurately predict the presence of metastatic melanoma (MM) and has been used to identify patients with occult metastases. We present an analysis of the sensitivity and specificity of standard pathological techniques including intraoperative frozen section, permanent section, and immunohistochemistry in diagnosing MM within the SLN.Methods: Sixty-nine consecutive patients with primary malignant melanoma thickness of .1.0 mm or thinner lesions invading the reticular dermis (Clark level IV) who underwent SLN biopsy were reviewed. Lymph nodes were examined intraoperatively by frozen section (FS), permanent section (H&E), and by immunohistochemistry (IH) for S-100 protein and HMB45.Results: MM was found in 14 of 69 cases (20%). Permanent section H&E was performed in all cases, FS in 64 cases, and IH in 65 cases. FS analysis diagnosed MM in 4 of 14 cases (29%), was suspicious in 2 of 14 (14%), and falsely negative (FN) in 8 of 14 (57%) ultimately found to be positive with further workup. Within the FN group, MM was identified on review of the original FS slides in 3 of 8 cases (38%). Furthermore, within the FN group, the remaining 5 cases were identified as positive for MM by either permanent and/or deeper H&E sections and IH. IH alone with permanent H&E sections would have diagnosed MM in only 8 of 10 cases (80%) that were FS negative or suspicious. In no cases was MM identified by IH alone with the permanent and deeper H&E sections being negative. It is noteworthy that no false-positive cases were identified.Conclusions: Intraoperative FS has low sensitivity in identifying MM within the SLN. IH alone does not increase the diagnostic yield. A combination of permanent H&E sections with deeper levels and S-100 and HMB45 IH dramatically increases the overall diagnostic sensitivity of SLN biopsy. Definitive diagnosis should await permanent H&E sections and IH staining.     

Transduced viral IL-10 is exocytosed from lacrimal acinar secretory vesicles in a myosin-dependent manner in response to carbachol

The purpose of this study was to determine the intracellular trafficking and release pathways for the therapeutic protein, viral IL-10 (vIL-10), from transduced acinar epithelial cells from rabbit lacrimal gland. Primary cultured rabbit lacrimal gland acinar cells (LGACs) were transduced with adenovirus serotype 5 containing viral interleukin-10 (AdvIL-10). The distribution of vIL-10 was assessed by confocal fluorescence microscopy. Carbachol (CCH)-stimulated release of vIL-10 was quantified by ELISA. vIL-10 localization and exocytosis was probed in response to treatments with agents modulating actin- and myosin-based transport. vIL-10 immunoreactivity was detected in large intracellular vesicles in transduced LGAC. vIL-10 was partially co-localized with biosynthetic but not endosomal compartment markers. vIL-10 release was sensitive to CCH, and the kinetics of release showed an initial burst phase that was similar but not identical to that of the secretory protein, β-hexosaminidase. Disassembly of actin filaments with latrunculin B significantly increased CCH-stimulated vIL-10 secretion, suggesting that vIL-10 was released from stores sequestered beneath the subapical actin barrier. That release required the activity of actin-dependent myosin motors previously implicated in secretory vesicle exocytosis was confirmed by findings that CCH-stimulated vIL-10 release was reduced by inhibition of non-muscle myosin 2 and myosin 5c function, using ML-7 and overexpression of dominant negative myosin 5c, respectively. These results suggest that the majority of vIL-10 transgene product is packaged into a subpopulation of secretory vesicles that utilize actin-dependent myosin motors for aspects of actin coat assembly, compound fusion and exocytosis at the apical plasma membrane in response to CCH stimulation.     

Doppler velocimetry determined redistribution of fetal blood flow: Correlation with growth restriction in diamniotic monochorionic and dizygotic twins

OBJECTIVE: Our purpose was to study fetal growth and blood flow distribution in diamniotic monochorionic compared with dizygotic (diamniotic dichorionic) twins by use of Doppler velocimetry of the umbilical artery and middle cerebral artery. STUDY DESIGN: Study candidates were divided into group A, consisting of 33 pairs (66 fetuses) of diamniotic monochorionic twins, and group B, 50 pairs (100 fetuses) of diamniotic dichorionic twins. Diamniotic monochorionic placentation was confirmed by microscopic placental examination for group A. Diamniotic dichorionic placentation was ensured for group B by selecting only twins with different-sex pairs (dizygotic twins). Targeted ultrasonography with biometry was performed in each twin, and Doppler recordings of the umbilical artery and middle cerebral artery were obtained. Waveforms were analyzed and the systolic/diastolic ratio, the resistance index, and a measure of blood flow redistribution (brain-sparing effect), the cerebral/placental ratio, was calculated for each fetus. Growth status at birth was assessed by the number of small-for-gestational-age infants (≤10th percentile), low-birth-weight infants (≤25th percentile), and percent of growth discordance between twins. Intertwin differences were assessed by Δ values (value of larger twin minus value of smaller twin). RESULTS: Diamniotic monochorionic compared with dizygotic twins demonstrated a significantly greater probability of blood flow redistribution. For the study population as a whole, the brain-sparing effect was noted in 67% of small-for-gestational-age babies and only 7% of non-small-for-gestational-age infants (p ≤ 0.001). For the diamniotic monochorionic pregnancies blood flow redistribution occurred in 6 of 10 small-for-gestational-age infants (60%) and 6 of 46 non-small-for-gestational-age infants (13%). In the diamniotic monochorionic group small-for-gestational-age compared with non-small-for-gestational-age infants were more likely to show blood flow redistribution, which was the result of significantly decreased resistance in the middle cerebral artery and significantly increased resistance in the umbilical artery. Small-for-gestational-age infants (≤10th percentile) occurred much less frequently in the dizygotic group. Two of two small-for-gestational-age infants in the dizygotic group showed blood flow redistribution. Although the extremes of birth weight were more common in the diamniotic monochorionic group, both groups had relatively large numbers of small babies with birth weights in the lower 25th percentile (50.0% for diamniotic monochorionic and 44.0% for dizygotic twins, not significant). However, 42.3% (11/26) of diamniotic monochorionic twins who were in the low-birth-weight group showed blood flow redistribution compared with only 3.3% (1/30) whose birth weights were ≥25th percentile (p ≤ 0.001). In the dizygotic twins 10% of lower-birth-weight infants redistributed blood flow compared with 1% in the higher-birth-weight group, a nonsignificant difference. Diamniotic monochorionic compared with dizygotic twins were delivered earlier (32.9 weeks vs 34.8 weeks, p ≤ 0.001), were smaller (1832 gm vs 2304 gm, p ≤ 0.001), showed higher birth weight discordance (29.8% vs 14%, p ≤ 0.05), and had greater numbers (19.7% vs 2.3%, p ≤ 0.01) of infants at ≤10th percentile birth weight. CONCLUSIONS: Diamniotic monochorionic twins from the lower-birth-weight groups more often show blood flow redistribution compared with dizygotic twins of similar low birth weights. Placental vascular connections and the attendant hemodynamic changes in the fetuses of diamniotic monochorionic twins probably account for this difference. Brain-sparing events occur commonly without clinical twin transfusion syndrome in this group. These findings have implications for management. (Am J Obstet Gynecol 1998;178:1359-67.)