High alveolar surface tension increases clearance of technetium 99m diethylenetriamine-pentaacetic acid.

The effect of high alveolar surface tension on alveolar epithelial permeability was studied in anesthetized closed-chest mongrel dogs. Alveolar surface tension was elevated by displacement of pulmonary surfactant from the alveolar hypophase by the aerosolized detergent dioctyl sodium sulfosuccinate (OT). After measurement of baseline hemodynamics, arterial blood gases, and airway pressure, the dogs were separated into groups: Group I inhaled a 1% solution of OT (15 mg/kg) in a vehicle of equal parts saline and ethanol; group II inhaled the same volume of vehicle without OT. The pulmonary clearance of technetium 99m diethylenetriamine-pentaacetic acid (99mTc-DTPA) (half-time in minutes) was studied immediately after aerosol (OT and vehicle) delivery and compared with that of historical control values. No change was seen in arterial blood gases and airway pressure after vehicle inhalation, whereas OT caused a marked fall in arterial oxygen tension and increase in airway pressure. Vehicle inhalation effected only a slight increase in DTPA clearance, whereas OT significantly reduced half-time over control and group II. These data suggest that high alveolar surface tension increases alveolar epithelial permeability.     

Calcium decreases transparency of homogenate from lens cortex and has no effect on nucleus

We studied the effects of calcium on transparency in homogenates of cortical and nuclear cells from calf lenses. Calcium was mixed into samples of homogenate to final concentrations between 0 and 50 mM and the transparency of the calcium-treated homogenates was measured using laser transmittance. In the presence of 10 mM calcium, the transmittance of cortical homogenate decreased 50% while the nuclear homogenate lost less than 4% transmittance after 24 h at 37 degrees C. To better understand the contribution of cytoplasm and membranes to opacity, the nuclear and cortical homogenates were centrifuged to separate membranes from the cytoplasm. When 10 mM calcium was added to cortical homogenate which was then centrifuged, the transmittance of the membrane fraction decreased nearly 60%, while the fraction without membrane decreased only 10%. The strong effect of calcium on the membrane fraction was accompanied by an increase in specific gravity of membranes from 1.23 to 1.32. Ten- and 20 mM calcium had no effect on transparency of membranes or cytoplasm separated from nuclear homogenate, and 50 mM calcium produced only a slight opacity. The results indicate that an effect on membrane-protein interactions may be important in the loss of transparency produced by calcium in cells of lens cortex.     

Techniques of splenic preservation using fibrin glue

Fibrin glue (FG) was used to achieve hemostasis of 16 splenic injuries in 14 patients. The etiologies of injury included five gunshot wounds, two stab wounds, four iatrogenic injuries, and five patients with blunt splenic trauma. The intraoperative blood loss averaged 1.8 +/- 2.4 (SD) liters and patients were transfused 3 +/- 2 units of blood perioperatively. The amount of FG required to achieve splenic hemostasis averaged 11 +/- 8 ml and varied directly with the grade of injury. One patient with a splenic hilar vascular injury (Grade V) underwent splenectomy following failure to achieve complete hemostasis despite the use of 25 ml of FG. All other splenic injuries were successfully managed using less than 25 ml of FG. Postoperative computerized tomographic (CT) scanning, performed in ten patients, was negative for rebleeding or abscess formation. The overall splenic salvage rate was 86%. FG was effective in achieving hemostasis of both superficial and deep splenic injuries. Its use as an adjunct in trauma surgery should result in increased splenic salvage rates compared with that obtained using conventional surgical techniques.     

Acute psychoses: A proposed diagnosis for ICD-11 and DSM-V

This paper concerns the diagnostic classification of nonaffective acute remitting psychosis (NARP), which we also term acute brief psychosis. We argue that NARP can be delineated from both schizophrenia and the affective psychoses and considered as a single diagnosis. As indicated by the term NARP, four criteria would be central to the diagnosis: 1. nonaffective, 2. acute onset (over less than two weeks), 3. recovery within a brief duration (less than six months), and 4. psychosis broadly defined. We review the rationale and the empirical evidence for this proposed classification.     

Evaluation of ambulatory care training by graduates of internal medicine residencies

In 1984, 154 physicians who had completed residencies in internal medicine at 15 major teaching hospitals in 1982 evaluated their residency training in ambulatory care. A majority of the physicians would have liked more experience in practical areas related to career planning and office management, more input from subspecialties such as orthopedics and dermatology, greater knowledge about the management of psychosocial problems, and more information about exercise and nutrition. Although many physicians also wanted more time devoted to several other topics, less than 20 percent recommended spending less time on 26 of the 27 topics being evaluated. Since these recommendations are similar to those reported in evaluation studies published over the past 25 years, it appears that training programs in internal medicine have not been successful in restructuring their curricula to meet many of the needs of practicing physicians.     

Regulation of COX-2 mediates acid-induced bone calcium efflux in vitro.

Chronic metabolic acidosis induces net Ca efflux from bone; this osteoclastic bone resorption is mediated by increased osteoblastic prostaglandin synthesis. Cyclooxygenase, the rate-limiting enzyme in prostaglandin synthesis, is present in both constitutive (COX-1) and inducible (COX-2) forms. We report here that acidosis increases both osteoblastic RNA and protein levels for COX-2 and that genetic deficiency or pharmacologic inhibition of COX-2 significantly reduces acid-induced Ca efflux from bone. INTRODUCTION: Incubation of neonatal mouse calvariae in medium simulating physiologic metabolic acidosis induces an increase in osteoblastic prostaglandin E2 (PGE2) release and net calcium (Ca) efflux from bone. Increased PGE2 is necessary for acid-induced bone resorption, because inhibition of cyclooxygenase activity with indomethacin significantly decreases not only PGE2 production but also Ca release. Cyclooxygenase is present in both constitutive (COX-1) and inducible (COX-2) forms. Because COX-2 activity has been implicated in several forms of pathological bone resorption, we tested the hypothesis that COX-2 is critical for acid-induced, cell-mediated bone Ca efflux. MATERIALS AND METHODS: To determine the effect of metabolic acidosis on COX-2 RNA and protein, primary cells isolated from neonatal CD-1 mouse calvariae were cultured in neutral (Ntl) or physiologically acidic medium (Met). RNA levels for COX-2 and COX-1 were measured by quantitative real-time PCR. Levels of COX-2 and COX-1 protein were measured by immunoblot analysis. To determine the effect of acidosis on bone Ca efflux in genetically deficient COX-2 mice, mice heterozygous for the COX-2 knockout (strain B6;129S7-Ptgs2(tm1Jed)/J) were used as breeders, and neonatal calvariae were cultured in Ntl or Met. To determine the effects of the specific COX-2 inhibitor, NS398, on acid-induced bone resorption, CD-1 calvariae were incubated in Ntl or Met with or without NS398 (1 microM). Medium PGE2 was assayed by ELISA. RESULTS: Incubation of mouse calvarial cells in Met significantly increased COX-2 RNA and protein levels without a change in COX-1. Increased COX-2 protein levels in response to Met were also observed in cultured calvariae. Acid-induced, cell-mediated Ca efflux from B6;129S7-Ptgs2(tm1Jed)/J calvariae was dependent on genotype. From 0 to 24 h, when physicochemical Ca efflux predominates, Met significantly increased net Ca efflux in all genotypes. After 24 h, when cell-mediated Ca efflux predominates, Met induced greater Ca efflux from (+/+) than from (+/-), and there was no increase from (-/-). In calvariae from CD-1 mice, NS398 significantly inhibited both the acid-induced increase in PGE2 and Ca release. CONCLUSIONS: The specific acid-induced increase in COX-2 RNA and protein levels and the dependency of the increased Ca efflux on COX-2 activity, as determined by both genetic deficiency and pharmacologic inhibition, show that COX-2 is critical for acid-induced, cell-mediated bone resorption.     

Familial stenosis of the pulmonary artery branches with a JAG1 mutation.

Although most congenital heart defects are isolated abnormalities of embryonic development, with little genetic contribution, a small number are components of syndromes. In such cases, an accurate diagnosis has important implications for individual prognosis and familial genetic counseling. Alagille syndrome (AGS) is a dominantly inherited multisystem developmental disorder, which primarily affects the liver, heart, eyes, skeleton, and face. In recent years, the identification of the AGS gene has drawn attention to the existence of subclinical carriers, and broadened the spectrum of phenotypical variation associated with this syndrome. The authors present a case of mother and son with benign stenosis of the pulmonary artery branches. Subtle facial aspects suggested the diagnosis of AGS, which was confirmed by molecular analysis. Relevant clinical investigations and diagnostic implications are discussed.     

Successful immune reconstitution decreases leukemic relapse and improves survival in recipients of unrelated cord blood transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) is established therapy for selected patients with acute leukemia. After transplantation, antileukemic immune responses are believed to eliminate residual leukemia cells and decrease the likelihood of relapse. However, the clinical effect of successful antigen-specific immune reconstitution after HSCT on the likelihood of leukemic relapse and overall survival is not known. Pediatric recipients of unrelated cord blood transplants who underwent transplantation for acute leukemia were sequentially evaluated for their development of antigen-specific T-lymphocyte immunity to herpes viruses. The clinical effect of a positive antigen-specific response on relapse-free survival was determined. The presence of an antigen-specific response resulted in a relapse-free survival advantage (P = .0001), which was primarily due to a decrease in leukemic relapse (P = .003). Proportional hazards modeling for time to relapse and time to relapse or death defined 3 variables that were strongly associated with a poor outcome: female gender, poor remission status before transplantation, and negative antigen-specific T-lymphocyte proliferation. Notably neither acute nor chronic graft-versus-host disease had any effect on the incidence of leukemic relapse. Successful antigen-specific immune reconstitution after unrelated cord blood transplantation results in decreased leukemic relapse and improved overall survival.     

Association Between Outpatient Follow-Up and Pediatric Emergency Department Asthma Visits

Background. The National Heart, Lung, and Blood Institute (NHLBI) guidelines recommend that patients receive a follow-up outpatient asthma visit after being discharged from an emergency department (ED) for asthma. Objective. To measure the frequency of follow-up outpatient asthma visits and its association with repeat ED asthma visit. Design. We conducted a retrospective cohort study of children with asthma using claims data from a university-based managed care organization from 01 1998 to 10 2000. We performed a multivariate survival analysis using Cox proportional hazards model to determine the effect of follow-up outpatient asthma visits on the likelihood of a repeat ED asthma visit, after controlling for severity of illness, patient age, gender, insurance, and the specialty of the primary care provider. Results: A total of 561 children had 780 ED asthma visits. Of these, 103 (17%) had a repeat ED asthma visit within 1 year. Almost two-thirds of children (66%) did not receive outpatient follow-up for asthma within 30 days of an ED asthma visit. Outpatient asthma visits within 30 days of an ED asthma visit are associated with an increased likelihood (relative risk = 1.80; 95% confidence interval 1.19, 2.72) for repeat ED asthma visits within 1 year. Conclusions. Most patients do not have outpatient follow-up after an ED asthma visit. However, those patients that present for outpatient follow-up have an increased likelihood for repeat ED asthma visits. For the primary care provider, these outpatient follow-up visits signal an increased risk that a patient will return to the ED for asthma and are a key opportunity to prevent future ED asthma visits.     

DLCO/Q and diffusion limitation at rest and on exercise in patients with interstitial fibrosis

Pulmonary diffusing capacity for carbon monoxide (DLCO) and pulmonary capillary blood flow (Qp) were measured on exercise in patients with a low DLCO with the aim of predicting, from the overall DL/Qp ratio, diffusion limitation for oxygen and relating it to the fall in arterial oxygen saturation actually observed. Five patients with cryptogenic fibrosing alveolitis (DLCO ranging from 20-54% predicted normal) exercised for 5 min at a work load equal to 60% of their maximum (45 to 90 watts). At 5 min (and previously at rest) they rebreathed rapidly for 15 sec from a 1.0 L bag containing helium (He), sulphur hexafluoride (SF6) and freon-22, 30% oxygen in argon and less than 1 ppm 11C-labelled carbon monoxide. Pulmonary capillary blood flow (Qp) and diffusing capacity (DLCO) were measured from flow-weighted breath-by-breath concentrations of freon-22 and 11CO, after correction for gas mixing delays (using He and SF6). Oxygen saturation (SaO2) (ear oximetry), MO2 and MCO2 and cardiac frequency were measured. PAO2 (ideal) was derived and mixed venous O2 saturation and content were calculated (Fick); PaO2 and PVO2 were derived from standard dissociation curves. For comparison, DLCO and Qp were measured in a similar fashion in five normal subjects exercising at 60 watts. Mean DLCO in patients with fibrosis was 9.62 (SD 2.88) ml.min-1, mm Hg-1 on exercise and mean Qp was 10.48 (SD 1.79) L.min-1 giving mean DLCO/Q ratios of 0.92 (SD 0.28). At 60 watts mean DLCO/Qp in normal subjects was 2.54 (SD 0.3), 2.76-times greater than in patients. SaO2% fell in patients by 3-15% on exercise. Predictions of alveolar-end capillary PO2 gradients from these overall DL/Q gradients showed that diffusion limitation accounted for 99% of the alveolar-arterial PO2 gradient on exercise in fibrosing alveolitis. Hughes (1991 Respir. Physiol. 83:167-178) [corrected] suggests that this simple approach overestimates the contribution of diffusion limitation by about 30%.