Effects of vaporized perfluorocarbon on pulmonary blood flow and ventilation/perfusion distribution in a model of acute respiratory distress syndrome.

BACKGROUND: Perfluorocarbon (PFC) liquids are known to improve gas exchange and pulmonary function in various models of acute respiratory failure. Vaporization has been recently reported as a new method of delivering PFC to the lung. Our aim was to study the effect of PFC vapor on the ventilation/perfusion (VA/Q) matching and relative pulmonary blood flow (Qrel) distribution. METHODS: In nine sheep, lung injury was induced using oleic acid. Four sheep were treated with vaporized perfluorohexane (PFX) for 30 min, whereas the remaining sheep served as control animals. Vaporization was achieved using a modified isoflurane vaporizer. The animals were studied for 90 min after vaporization. VA/Q distributions were estimated using the multiple inert gas elimination technique. Change in Qrel distribution was assessed using fluorescent-labeled microspheres. RESULTS: Treatment with PFX vapor improved oxygenation significantly and led to significantly lower shunt values (P < 0.05, repeated-measures analysis of covariance). Analysis of the multiple inert gas elimination technique data showed that animals treated with PFX vapor demonstrated a higher VA/Q heterogeneity than the control animals (P < 0.05, repeated-measures analysis of covariance). Microsphere data showed a redistribution of Qrel attributable to oleic acid injury. Qrel shifted from areas that were initially high-flow to areas that were initially low-flow, with no difference in redistribution between the groups. After established injury, Qrel was redistributed to the nondependent lung areas in control animals, whereas Qrel distribution did not change in treatment animals. CONCLUSION: In oleic acid lung injury, treatment with PFX vapor improves gas exchange by increasing VA/Q heterogeneity in the whole lung without a significant change in gravitational gradient.     

A technique for intraoperative arteriography following carotid endarterectomy

This technique provides a simple and reliable means of obtaining an operative arteriogram after carotid endarterectomy. Detection of unsuspected abnormalities before the wound is closed allows the surgeon to correct any abnormalities immediately with hopes of decreasing the incidence of postoperative neurological deficits.     

Treatment results following the pull-through operation and continence-improving operations in high anal and rectum atresia

Of 174 patients with anorectal malformations, among them 71 children with high atresia, 59 patients could be followed-up. 57% were entirely incontinent according to electromanometrical findings. These patients necessarily needed sphincter-replacement operations to improve the function of the sphincter-apparatus. Eighty-one sphincter-replacement operations were performed in 68 patients, among them 56 gracilis transplantations, 12 palmaris-longus transplantations, and 4 stalked smooth muscle transplantations. All sphincter replacement operations improved continence considerably.     

Inherited disorders of 3-methylcrotonyl CoA carboxylation

The clinical course of 4 patients who had reduced activities of 3-methylcrotonyl CoA carboxylase (also called 3-methylcrotonylglycinuria) is described. Two children presented with a metabolic acidosis, one in the neonatal period and the other with episodes of acidosis that started in the second year of life. In the other 2 children neurological symptoms were prominent, one having infantile spasms and the other developmental regression with a skin rash and alopecia. Three of the children responded well to oral biotin and dietary protein restriction but the fourth, despite a biochemical response to biotin, has a severe neurological handicap. The clinical presentation of inborn errors of 3-methylcrotonyl CoA carboxylase is variable. Metabolic acidosis may not be conspicuous and instead neurological features may predominate.     

Vaginal reconstruction in the fibrotic pelvis

Vaginal reconstruction was performed in 7 patients who had developed vaginal stenosis as a result of extensive pelvic fibrosis following either pelvic irradiation (6 patients) or multiple vaginal procedures (1 patient). Six patients received split thickness skin grafts and 1 patient received an amnion graft in the creation of the neovagina. Five patients achieved a satisfactory final result. All of these patients were sexually active and described adequate sexual function. There was no serious morbidity associated with these procedures. Safe and successful vaginal reconstruction can be performed in a patient with a fibrotic pelvis.     

Prognostic Factors in Glioblastoma Multiforme 10 Years Experience of a Single Institution

Background: To analyze prognostic factors in patients with a glioblastoma multiforme treated in an academic institute over the last 10 years. Patients and Method: From 1988 to 1998, 198 patients with pathologically confirmed glioblastoma multiforme were analyzed. Five radiation schedules were used mainly based on pretreatment selection criteria: 1. 60 Gy in 30 fractions followed by an interstitial iridium-192 (Ir-192) boost for selected patients with a good performance and a small circumscribed tumor, 2. 66 Gy in 33 fractions for good performance patients, 3. 40 Gy in eight fractions or 4. 28 Gy in four fractions for poor prognostic patients and 5. no irradiation. Results: Median survival was 16 months, 7 months, 5.6 months, 6.6 months and 1.8 months for the groups treated with Ir-192, 66 Gy, 40 Gy, 28 Gy and the group without treatment, respectively. No significant improvement in survival was encountered over the last 10 years. At multivariate analysis patients treated with a hypofractional scheme showed a similar survival probability and duration of palliative effect compared to the conventionally fractionated group. The poor prognostic groups receiving radiotherapy had a highly significant better survival compared to the no-treatment group. Patients treated with an Ir-192 boost had a better median survival compared to a historical group matched on selection criteria but without boost treatment (16 vs 9.7 months, n. s.). However, survival at 2 years was similar. Analysis on pretreatment characteristics at multivariate analysis revealed age, neurological performance, addition of radiotherapy, total resection, tumor size post surgery and deterioration before start of radiotherapy (borderline) as significant prognostic factors for survival. Conclusion: Despite technical developments in surgery and radiotherapy over the last 10 years, survival of patients with a glioblastoma multiforme has not improved in our institution. The analysis of prognostic factors corresponded well with data from the literature. A short hypofractionated scheme seems to be a more appropriate treatment for patients with intermediate or poor prognosis as compared to a conventional scheme. The benefit in median survival for patients treated with an interstitial boost is partly explained by patient selection. Since there were no long-term survivors with this boost treatment, its clinical value, if there is one, is still limited. Hintergrund: Es wurden Prognosefaktoren bei Patienten mit Glioblastoma multiforme ermittelt, die über einen Zeitraum von 10 Jahren in einer Institution behandelt wurden. Patienten und Methoden: Die Analyse beruht auf 198 Patienten, die von 1988 bis 1998 nach histologischer Sicherung fünf verschiedenen Bestrahlungsschemata zugeführt wurden: 1. 60 Gy in 30 Fraktionen gefolgt von einem Ir-192-(LDR-)Boost bei selektierten Patienten mit gutem Performance-Status und kleinen Tumoren, 2. 66 Gy in 33 Fraktionen bei Patienten mit gutem Performance-Status, 3. 40 Gy in acht Fraktionen oder 4. 28 Gy in vier Fraktionen bei Patienten in schlechtem Allgemeinzustand, 5. keine Bestrahlung. Ergebnisse: Das mediane Überleben betrug 16 Monate für die Ir-192-Boost-Gruppe, 7 Monate nach 66 Gy, 5,6 Monate nach 40 Gy, 6,6 Monate nach 28 Gy und 1,8 Monate für unbehandelte Patienten. Über den Behandlungszeitraum von 10 Jahren waren keine signifikanten Verbesserungen der Überlebensraten zu verzeichnen. In der Multivarianzanalyse wiesen Patienten, die hypofraktioniert bestrahlt wurden, ähnliche Überlebenswahrscheinlichkeiten und Palliativeffekte auf wie Patienten nach konventioneller Bestrahlung. Die Strahlentherapie führte bei Patienten mit schlechtem Allgemeinzustand zu signifikanten Überlebenszeitverbesserungen im Vergleich zu Patienten ohne Behandlung. Verglichen mit einer historischen Kontrollgruppe ohne Ir-192-Boost-Bestrahlung hatten Patienten nach Ir-192-Boost-Bestrahlung nicht signifikante Verbesserungen der medianen Überlebensraten (16 Monate v. 9,7 Monate), wobei sich jedoch die 2-Jahres-Überlebensraten wieder angeglichen. In der Multivarianzanalyse waren Alter, neurologischer Status, Radiotherapie, totale Resektion, Resttumorgröße nach Resektion und Verschlecherung vor Anfang der Strahlentherapie (Grenzwert) für das Überleben signifikante Prognosefaktoren. Schlussfolgerungen: Trotz technischer Entwicklungen sowohl im Bereich der Neurochirurgie als auch der Radiotherapie verbesserten sich die Überlebensraten von Patienten mit Glioblastoma multiforme in den letzten 10 Jahren in unserer Institution nicht. Die Analyse der Prognosefaktoren korreliert gut mit Angaben aus der Literatur. Für Patienten mit intermediärer oder schlechter Prognose ist ein abgekürztes hypofraktioniertes Bestrahlungsregime eine angemessene Therapieoption. Die beobachtete Verbesserung der medianen Überlebensraten nach Ir-192-Boost ist zumindest teilweise durch eine Patientenselektion erklärbar. Da diese Behandlungsform zu keinem Langzeitüberleben führt, ist der klinische Stellenwert weiterhin unklar.     

Prognostic Factors in Glioblastoma Multiforme 10 Years Experience of a Single Institution

BACKGROUND: To analyze prognostic factors in patients with a glioblastoma multiforme treated in an academic institute over the last 10 years. PATIENTS AND METHOD: From 1988 to 1998, 198 patients with pathologically confirmed glioblastoma multiforme were analyzed. Five radiation schedules were used mainly based on pretreatment selection criteria: 1. 60 Gy in 30 fractions followed by an interstitial iridium-192 (Ir-192) boost for selected patients with a good performance and a small circumscribed tumor, 2. 66 Gy in 33 fractions for good performance patients, 3. 40 Gy in eight fractions or 4. 28 Gy in four fractions for poor prognostic patients and 5. no irradiation. RESULTS: Median survival was 16 months, 7 months, 5.6 months, 6.6 months and 1.8 months for the groups treated with Ir-192, 66 Gy, 40 Gy, 28 Gy and the group without treatment, respectively. No significant improvement in survival was encountered over the last 10 years. At multivariate analysis patients treated with a hypofractionated scheme showed a similar survival probability and duration of palliative effect compared to the conventionally fractionated group. The poor prognostic groups receiving radiotherapy had a highly significant better survival compared to the no-treatment group. Patients treated with an Ir-192 boost had a better median survival compared to a historical group matched on selection criteria but without boost treatment (16 vs 9.7 months, n.s.). However, survival at 2 years was similar. Analysis on pretreatment characteristics at multivariate analysis revealed age, neurological performance, addition of radiotherapy, total resection, tumor size post surgery and deterioration before start of radiotherapy (borderline) as significant prognostic factors for survival. CONCLUSION: Despite technical developments in surgery and radiotherapy over the last 10 years, survival of patients with a glioblastoma multiforme has not improved in our institution. The analysis of prognostic factors corresponded well with data from the literature. A short hypofractionated scheme seems to be a more appropriate treatment for patients with intermediate or poor prognosis as compared to a conventional scheme. The benefit in median survival for patients treated with an interstitial boost is partly explained by patient selection. Since there were no long-term survivors with this boost treatment, its clinical value, if there is one, is still limited.     

Policy implications for implementing evidence-based practices.

The authors describe the policy and administrative-practice implications of implementing evidence-based services, particularly in public-sector settings. They review the observations of the contributors to the evidence-based practices series published throughout 2001 in Psychiatric Services. Quality and accountability have become the watchwords of health and mental health services; evidence-based practices are a means to both ends. If the objective of accountable, high-quality services is to be achieved by implementing evidence-based practices, the right incentives must be put in place, and systemic barriers must be overcome. The authors use the framework from the U.S. Surgeon General's 1999 report on mental health to describe eight courses of action for addressing the gap between science and practice: continue to build the science base; overcome stigma; improve public awareness of effective treatments; ensure the supply of mental health services and providers; ensure delivery of state-of-the-art treatments; tailor treatment to age, sex, race, and culture; facilitate entry into treatment; and reduce financial barriers to treatment.     

Inhibitors of aminoacyl-tRNA synthetases as novel anti-infectives

Resistance to existing antibiotics has emerged as a major problem in healthcare. Novel antibiotics for which bacteria have not yet acquired resistance need to be developed to combat drug-resistant pathogens. Aminoacyl-tRNA synthetases are leading targets for novel anti-infectives. The validation of aminoacyl-tRNA synthetases as drug targets for anti-infectives has been established in an animal system. Using several conceptually distinct approaches, new inhibitors of synthetases have been developed as drug prototypes.