Soil temperature moderates grapevine carbohydrate reserves after bud break and conditions fruit set responses to photoassimilatory stress.

In cultivated grapevines (Vitis vinifera L.), suboptimal photoassimilatory conditions during flowering can lead to inflorescence necrosis and shedding of flowers and young ovaries and, consequently, poor fruit set. However, before this study it was not known whether carbohydrate reserves augment fruit set when concurrent photoassimilation is limited. Carbohydrate reserves are most abundant in grapevine roots and soil temperature moderates their mobilisation. Accordingly, we grew potted Chardonnay grapevines in soil at 15°C (cool) or 26°C (warm) from bud break to the onset of flowering to manipulate root carbohydrate reserve status. Then to induce photoassimilatory responses we subjected the plants to low (94µmolmol-1) CO2 or ambient (336µmolmol-1) CO2 atmospheres during fruit setting. Analyses of photoassimilation and biomass and carbohydrate reserve distribution confirmed that fruit set was limited by concurrent photoassimilation. Furthermore, the availability of current photoassimilates for inflorescence development and fruit set was conditioned by the simultaneous demands for shoot and root growth, as well as the restoration of root carbohydrate reserves. Results indicate that great seasonal variability in grapevine fruit set is a likely response of cultivated grapevines to photoassimilatory stresses, such as shading, defoliation and air temperature and to variations in carbohydrate reserve status before flowering.

Long-term results of microwave thermotherapy for symptomatic benign prostatic hyperplasia.

PURPOSE: To study the long-term outcomes of men with moderately severe symptomatic benign prostatic hyperplasia (BPH) who were treated with transurethral microwave thermotherapy (TUMT) with the Dornier Urowave machine. PATIENTS AND METHODS: A total of 220 patients (mean age 66.2 years) with clinical BPH, an American Urological Association (AUA) Symptom Score of >or=13, and a peak urinary flow rate (Qmax) of

Transient induction of TGF-alpha disrupts lung morphogenesis, causing pulmonary disease in adulthood.

Clinical studies have associated increased transforming growth factor (TGF)-alpha and EGF receptor with lung remodeling in diseases including bronchopulmonary dysplasia (BPD). BPD is characterized by disrupted alveolar and vascular morphogenesis, inflammation, and remodeling. To determine whether transient increases in TGF-alpha are sufficient to disrupt postnatal lung morphogenesis, we utilized neonatal transgenic mice conditionally expressing TGF-alpha. Expression of TGF-alpha from postnatal days 3 to 5 disrupted postnatal alveologenesis, causing permanent enlargement of distal air spaces in neonatal and adult mice. Lung volume-to-body weight ratios and lung compliance were increased in adult TGF-alpha transgenic mice, whereas tissue and airway elastance were reduced. Elastin fibers in the alveolar septae were fragmented and disorganized. Pulmonary vascular morphogenesis was abnormal in TGF-alpha mice, with attenuated and occasionally tortuous arterial branching. The ratios of right ventricle weight to left ventricle plus septal weight were increased in TGF-alpha mice, indicating pulmonary hypertension. Electron microscopy showed gaps in the capillary endothelium and extravasation of erythrocytes into the alveolar space of TGF-alpha mice. Hemorrhage and inflammatory cells were seen in distal air spaces at 1 mo of age. In adult TGF-alpha mice, alveolar remodeling, nodules, proteinaceous deposits, and inflammatory cells were seen. Immunostaining for pro-surfactant protein C showed that type II cells were abundant in the nodules, as well as neutrophils and macrophages. Trichrome staining showed that pulmonary fibrosis was minimal, apart from areas of nodular remodeling in adult TGF-alpha mice. Transient induction of TGF-alpha during early alveologenesis permanently disrupted lung structure and function and caused chronic lung disease.

Dose-dependent lung remodeling in transgenic mice expressing transforming growth factor-alpha.

Transgenic mice overexpressing human transforming growth factor-alpha (TGF-alpha) develop emphysema and fibrosis during postnatal alveologenesis. To assess dose-related pulmonary alterations, four distinct transgenic lines expressing different amounts of TGF-alpha in the distal lung under control of the surfactant protein C (SP-C) promoter were characterized. Mean lung homogenate TGF-alpha levels ranged from 388 +/- 40 pg/ml in the lowest expressing line to 1,247 +/- 33 pg/ml in the highest expressing line. Histological assessment demonstrated progressive alveolar airspace size changes that were more severe in the higher expressing TGF-alpha lines. Pleural and parenchymal fibrosis were only detected in the highest expressing line (line 28), and increasing terminal airspace area was associated with increasing TGF-alpha expression. Hysteresis on pressure-volume curves was significantly reduced in line 28 mice compared with other lines of mice. There were no differences in bronchoalveolar lavage fluid cell count or differential that would indicate any evidence of lung inflammation among all transgenic lines. Proliferating cells were increased in line 28 without alterations of numbers of type II cells. We conclude that TGF-alpha lung remodeling in transgenic mice is dose dependent and is independent of pulmonary inflammation.

Use of the internet for self-education by patients with prostate cancer.

OBJECTIVES: To define use of the Internet for self-education by a cohort of patients with prostate cancer and to arrive at some relevant recommendations for the practicing urologist. Little has been published about patient use of the Internet in investigating their health conditions, specifically prostate cancer. METHODS: In April 1999, a self-administered, anonymous questionnaire was mailed to 490 men with the diagnosis of prostate cancer. Institutional ethics approval was obtained. Standard statistical analyses were performed. RESULTS: Of 490 questionnaires mailed, a total of 312 (63.7%) were available for analysis. Forty-eight percent of patients were 60 to 69 years old. Fifty-two percent of patients had never used a computer, and 25% described daily use. Only 35% of this cohort had used the Internet. Ninety-one patients had used the Internet to obtain information about prostate cancer, with 53 doing so after diagnosis but before deciding on treatment. Twenty-eight patients stated that Internet information influenced their decision about treatment. Not surprisingly, patients were more likely to use the Internet for health information if they were younger, had a higher education level, owned a personal computer, and had prior computing experience. Most patients could not recall the exact web sites they had visited but tended to recall the sites of some well-known institutions. CONCLUSIONS: In this Canadian cohort study, we found a substantial (and most likely, rapidly increasing) number of patients used the Internet to obtain health information. This information may influence patients' decisions regarding treatment and, as urologists, we should participate in the development of web sites directed toward shared decision-making. A list of practical recommendations has been formulated.

Functional genomics of oxidant-induced lung injury.

In summary, acute lung injury is a severe (>40% mortality) respiratory disease associated with numerous precipitating factors. Despite extensive research since its initial description over 30 years ago, questions remain about the basic pathophysiological mechanisms and their relationship to therapeutic strategies. Histopathology reveals surfactant disruption, epithelial perturbation and sepsis, either as initiating factors or as secondary complications, which in turn increase the expression of cytokines that sequester and activate inflammatory cells, most notably, neutrophils. Concomitant release of reactive oxygen and nitrogen species subsequently modulates endothelial function. Together these events orchestrate the principal clinical manifestations of the syndrome, pulmonary edema and atelectasis. To better understand the gene-environmental interactions controlling this complex process, we examined the relative sensitivity of inbred mouse strains to acute lung injury induced by ozone, ultrafine PTFE, or fine particulate NiSO4 (0.2 microm MMAD, 15-150 microg/m3). Measuring survival time, protein and neutrophils in bronchoalveolar lavage, lung wet: dry weight, and histology, we found that these responses varied between inbred mouse strains, and susceptibility is heritable. To assess the molecular progression of NiSO4-induced acute lung injury, temporal relationships of 8734 genes and expressed sequence tags were assessed by cDNA microarray analysis. Clustering of co-regulated genes (displaying similar temporal expression patterns) revealed the altered expression of relatively few genes. Enhanced expression occurred mainly in genes associated with oxidative stress, anti-proteolytic function, and repair of the extracellular matrix. Concomitantly, surfactant proteins and Clara cell secretory protein mRNA expression decreased. Genome wide analysis of 307 mice generated from the backcross of resistant B6xA F1 with susceptible A strain identified significant linkage to a region on chromosome 6 (proposed as Aliq4) and suggestive linkages on chromosomes 1, 8, and 12. Combining of these QTLs with two additional possible modifying loci (chromosome 9 and 16) accounted for the difference in survival time noted in the A and B6 parental strains. Combining these findings with those of the microarray analysis has enabled prioritization of candidate genes. These candidates, in turn, can be directed to the lung epithelium in transgenic mice or abated in inducible and constitutive gene-targeted mice. Initial results are encouraging and suggest that several of these mice vary in their susceptibility to oxidant-induced lung injury. Thus, these combined approaches have led to new insights into functional genomics of lung injury and diseases.

Pathogenomic mechanisms for particulate matter induction of acute lung injury and inflammation in mice.

To begin identifying genes controlling individual susceptibility to particulate matter, responses of inbred mouse strains exposed to nickel sulfate (NiSO4*) were compared with those of mice exposed to ozone (O3) or polytetrafluoroethylene (PTFE). The A strain was sensitive to NiSO4-induced lung injury (quantified by survival time), the C3H/He (C3) strain and several other strains were intermediate in their responses, and the C57BL/6 (B6) strain was resistant. The strains showed a pattern of response similar to the patterns of response to O3 and PTFE. The phenotype of A x B6 offspring (B6AF1) resembled that of the resistant B6 parental strain, with strains exhibiting sensitivity in the order A > C3 > B6 = B6AF1. Pathology was comparable for the A and B6 mice, and exposure to NiSO4 at 15 microg/m3 produced 20% mortality in A mice. Strain sensitivity for the presence of protein or neutrophils in lavage fluid differed from strain sensitivity for survival time, suggesting that they are not causally linked but are controlled by an independent gene or genes. In the B6 strain, exposure to nickel oxide (NiO) by instillation (40 to 1000 nm) or inhalation (50 nm) produced no changes, whereas inhalation of NiSO4 (60 or 250 nm) increased lavage proteins and neutrophils. Complementary DNA (cDNA) microarray analysis with 8,734 sequence-verified clones revealed a temporal pattern of increased oxidative stress, extracellular matrix repair, cell proliferation, and hypoxia, followed by a decrease in surfactant-associated proteins (SPs). Certain expressed sequence tags (ESTs), clustered with known genes, suggest possible coregulation and novel roles in pulmonary injury. Finally, locus number estimation (Wright equation) and a genomewide analysis suggested 5 genes could explain the survival time and identified significant linkage for a quantitative trait locus (QTL) on chromosome 6, Aliq4 (acute lung injury QTL4). Haplotype analysis identified an allelic combination of 5 QTLs that could explain the difference in sensitivity to acute lung injury between parental strains. Positional candidate genes for Aliq4 include aquaporin-1 (Aqp1), SP-B, and transforming growth factor-alpha (TGF-alpha). Transgenic mice expressing TGF-alpha were rescued from NiSO4 injury (that is, they had diminished SP-B loss and increased survival time). These findings suggest that NiSO4-induced acute lung injury is a complex trait controlled by at least 5 genes (all possibly involved in cell proliferation and surfactant function). Future assessment of these susceptibility genes (including evaluations of human synteny and function) could provide valuable insights into individual susceptibility to the adverse effects of particulate matter.

Measuring pleural fluid pH: high correlation of a handheld unit to a traditional tabletop blood gas analyzer.

UNLABELLED: STUDY PURPOSES: To survey hospital laboratories in the United States to determine methods used for measuring pleural fluid pH, and to compare pleural fluid pH values obtained with a traditional tabletop blood gas analyzer (BGA) to those obtained with a handheld analyzer. METHODS: Hospital laboratories nationwide were contacted by telephone to survey the methods used to measure pleural fluid pH. In a second phase, pleural fluid was prospectively collected from 19 pediatric and adult patients with pleural effusions, and pleural fluid pH was measured simultaneously with a traditional tabletop BGA and with a handheld unit. RESULTS: A total of 220 hospital laboratories were contacted by telephone, and 166 responded (75%). The methods for determining pleural fluid pH for all hospital laboratories were pH meter (35%; n = 59), BGA (32%; n = 53), and litmus paper (31%: n = 51); 2% (n = 3) did not perform the test. University hospitals were more likely to use a BGA, compared to community hospitals (p < 0.014) or children's hospitals (p < 0.001). In the comparison of pleural fluid measurements, the mean pH for the traditional BGA was 7.358 +/- 0.189, and the mean pH for the handheld unit was 7.382 +/- 0.203. The absolute difference between the two machines was 0.024 U, and the two methods were correlated (p < 0.01; r = 0.993; degrees of freedom = 36). CONCLUSION: Most hospital laboratories in the United States do not measure pleural fluid pH using a traditional BGA and use alternative methods that have previously been shown to be inaccurate. Pleural fluid pH obtained by a handheld unit has a high degree of correlation to that of a traditional tabletop BGA, and it offers a satisfactory alternative for laboratories reluctant to measure pleural fluid pH with a BGA.

Attenuation of acute lung injury in transgenic mice expressing human transforming growth factor-alpha.

Transforming growth factor-alpha (TGF-alpha) is produced in the lung in experimental and human lung diseases; however, its physiological actions after lung injury are not understood. To determine the influence of TGF-alpha on acute lung injury, transgenic mouse lines expressing differing levels of human TGF-alpha in distal pulmonary epithelial cells under control of the surfactant protein C gene promoter were generated. TGF-alpha transgenic and nontransgenic control mice were exposed to polytetrafluoroethylene (PTFE; Teflon) fumes to induce acute lung injury. Length of survival of four separate TGF-alpha transgenic mouse lines was significantly longer than that of nontransgenic control mice, and survival correlated with the levels of TGF-alpha expression in the lung. The transgenic line expressing the highest level of TGF-alpha (line 28) and nontransgenic control mice were then compared at time intervals of 2, 4, and 6 h of PTFE exposure for differences in pulmonary function, lung histology, bronchoalveolar lavage fluid protein and cell differential, and lung homogenate proinflammatory cytokines. Line 28 TGF-alpha transgenic mice demonstrated reduced histological changes, decreased bronchoalveolar lavage fluid total protein and neutrophils, and delayed alterations in pulmonary function measures of airway obstruction compared with those in nontransgenic control mice. Both line 28 and nontransgenic control mice had similar increases in interleukin-1beta protein levels in lung homogenates. In contrast, interleukin-6 and macrophage inflammatory protein-2 levels were significantly reduced in line 28 transgenic mice compared with those in nontransgenic control mice. In the transgenic mouse model, TGF-alpha protects against PTFE-induced acute lung injury, at least in part, by attenuating the inflammatory response.

Immunolocalization of transforming growth factor alpha and epidermal growth factor receptor in lungs of patients with cystic fibrosis.

Transforming growth factor alpha (TGF-alpha) is expressed in respiratory epithelial cells and alveolar macrophages during development and following lung injury. In the present study, the presence and sites of synthesis of TGF-alpha and its receptor, the epidermal growth factor receptor (EGF-R), were assessed in lung tissue from patients with severe lung disease caused by cystic fibrosis (CF). Lung sections from 24 individuals with CF, obtained at the time of lung transplantation, were compared to lung sections from five lung donors without CF. Cellular sites of TGF-alpha, EGF-R, and cellular sites of proliferation were assessed by immunohistochemistry. All CF lung sections contained multiple cell types with detectable TGF-alpha. Compared to control sections, intensity of TGF-alpha immunostaining in macrophages, airway epithelial cells, and peribronchial submucosal cells was increased. EGF-R was detected in respiratory epithelial and peribronchial stromal cells but not in alveolar macrophages. The intensity of EGF-R staining in CF lung tissue did not differ from that of controls. An increased number of cells expressing Ki-67 nuclear antigen was detected in peribronchial submucosal cells but not bronchiolar epithelial cells in the CF lungs. The increased expression of TGF-alpha in CF lung tissue supports the concept that TGF-alpha plays a role in paracrine/autocrine regulation of lung remodeling associated with injury and repair in the lungs of individuals with cystic fibrosis.

Complicated parapneumonic effusions in children caused by penicillin-nonsusceptible Streptococcus pneumoniae.

OBJECTIVE: To describe the clinical characteristics of complicated parapneumonic effusions (CPE) in children caused by Streptococcus pneumoniae nonsusceptible to penicillin (PCN-N) and compare their clinical outcome with CPE caused by penicillin-susceptible (PCN-S) organisms. DESIGN: Children with parapneumonic effusions were identified retrospectively between July 1992 and June 1996. Charts of patients with CPE were reviewed for data obtained at the time of hospital admission. In addition, outpatient charts and/or the families of children with CPE caused by PCN-N S pneumoniae were reviewed to identify specific risk factors associated with PCN-N organisms. RESULTS: Sixty-four cases of CPE were identified during the 4-year period. In 26 cases a bacterial pathogen was recovered, with S pneumoniae accounting for 23 of these isolates (88%). Of the 23 S pneumoniae cases, 17 were PCN-S and 6 cases were nonsusceptible. Complicated parapneumonic effusions caused by PCN-N S pneumoniae occurred in significantly younger patients than CPE that were PCN-S (2.1 years vs 7.9 years). Nonsusceptible effusions also had a higher incidence of bacteremia than PCN-S effusions (100% vs 29%). There were no significant differences between the two groups for duration of chest tube drainage, febrile days, oxygen use, and hospital stay. CONCLUSION: CPE caused by PCN-N S pneumoniae is associated with a younger age and higher rate of bacteremia than CPE caused by PCN-S strains. However, there were no significant differences in outcome measures between patients infected with susceptible or nonsusceptible organisms.

Quantitative Assessment of Polyethylene Component Position in a Mobile-Bearing Prosthetic Knee, Using a Single Radiograph.

Rationale and Objectives. To reduce tibio-femoral misalignment, the polyethylene bearing-component of a new knee prosthesis was allowed limited motion on the underlying metallic component. The object of the work presented here was to develop a suitable radiographic technique for quantifying the in-vivo position of the bearing. By collecting these data at discrete flexion angles, the functional operation of the prosthesis could be determined. Methods. The known geometries between landmarks on the two components were used to produce algorithms for reconstructing their spatial positions from a single radiograph. A custom-designed computer program utilized these algorithms to determine the relative translation and rotation of the polyethylene component. Results. This technique produced typical errors of 0.54 mm translation and 0.56 degrees rotation between the polyethylene component and the underlying metallic component. Conclusions. A practical method has been developed for assessing mobile-bearing motion, in vivo. This method can be applied to other prosthetic devices, or combinations of components, once the requirement for identifiable landmarks has been addressed. Clinical Relevance. Skeletal and soft-tissue changes in the pathological knee may produce abnormal rotations and translations in the transverse tibial plane. This technique is intended both to validate the design philosophy of a mobile-bearing prosthesis and to provide additional data on any pathological motions, which will have implications for future prosthetic designs.

Postnatal lung function and morphology in transgenic mice expressing transforming growth factor-alpha.

Developmental changes in lung morphology and physiology during postnatal alveolarization were assessed in transgenic mice expressing transforming growth factor-alpha (TGF-alpha) in pulmonary type II cells under control of the surfactant protein C gene promoter. TGF-alpha transcripts were identified in respiratory epithelial cells at 1 day of age to adulthood. Enlargement of alveolar airspaces and fibrosis were detected as early as 1 week of age, and the increased airspace progressed with advancing age. Specific lung compliance was significantly increased in lungs of transgenic mice by 2 weeks of age and was associated with airflow obstruction. Chronic expression of TGF-alpha in the lungs of newborn transgenic mice caused remodeling of the developing lung during the period of postnatal alveolarization, resulting in markedly enlarged parenchymal airspace, pulmonary fibrosis, and physiological abnormalities including airway obstruction and increased lung compliance.

Reversal of lung lesions in transgenic transforming growth factor alpha mice by expression of mutant epidermal growth factor receptor.

Transgenic mice expressing transforming growth factor alpha (TGF-alpha) in type II cells under control of the lung-specific surfactant protein-C (SP-C) promoter develop pulmonary fibrosis and marked airspace hypoplasia. To identify cellular signaling mechanisms involved in lesion formation, we generated transgenic mice expressing a mutant epidermal growth factor receptor lacking a portion of the intracytoplasmic domain (EGF-R-M) under control of the human SP-C promoter. Transcripts of the SP-C-EGF-R-M transgene were detected in distal bronchiolar and type II cells by in situ hybridization. The morphology of lungs from the SP-C-EGF-R-M transgenic mice was normal. Lung fibrosis was not detectable and airspace hypoplasia was significantly corrected in bitransgenic mice derived by breeding SP-C-TGF-alpha and SP-C-EGF-R-M mice. Correction of lung pathology in the bitransgenic mice occurred without altering the level of hTGF-alpha mRNA. To further demonstrate that reversal of TGF-alpha lesions required signaling through the EGF-R, SP-C-TGF-alpha transgenic mice were bred to mice homozygous for the wa-2 mutation which encodes a mutated EGF-R. TGF-alpha-induced lesions were reversed in homozygous wa-2 mice. Amelioration of TGF-alpha-dependent pulmonary lesions in SP-C-EGF-R-M mice or wa-2/wa-2 mice supports the concept that autocrine and paracrine signaling mediate fibrosis and airspace remodeling caused by TGF-alpha.

Pneumococcal pleural empyemas in children.

Empyema rarely complicates pneumonia. In a 361-bed regional pediatric hospital, 50 pleural empyemas were identified from 1988 through 1994; 17 (34%) occurred in the last 12 months of this period, for which the incidence was 3.3 per 100,000 of the population aged < or = 18 years (P < .05, chi 2 test). A significant seasonal prevalence was observed: 50% of cases occurred in the winter (P < .001, chi 2 test). In contrast with the findings of previous studies, in which empyemas predominantly occurred in infants, the median age of our patients was 7 years; underlying illnesses were present in only 10%, and all had community-acquired disease. Eighty-two percent had chest tubes inserted, 56% required a thoracotomy with pleural decortication, and 2% had a lobectomy. There were no deaths. Streptococcus pneumoniae was isolated in 40% of the cases; specimens in 44% of the cases were sterile. None of the empyemas were associated with Staphylococcus aureus or Haemophilus influenzae type b, and only one was caused by group A streptococcus. Among 13 S. pneumoniae isolates, the rate of resistance to penicillin was 15%; to erythromycin, 15%; to chloramphenicol, 31%; and to cefotaxime, 23%. The penicillin-resistance rate among blood and cerebrospinal fluid pneumococcal isolates was 17% during 1993-1994. Drug-resistant S. pneumoniae is now a recognized cause of pleural empyemas in children.

Geometrical properties of the ovine tibia: a suitable animal model to study the pin-bone interface in fracture fixation?

To determine whether dimensional scaling (relative to the human) is necessary for screwed pins used in externally applied fracture fixation studies on sheep, geometrical data were determined for six ovine tibiae. Each tibia was potted relative to a lengthwise reference axis and sectioned at 5 per cent length intervals over its central 80 per cent. Enlarged (280 per cent) images of each cross-section were digitized at 1 mm increments around the periphery of the periosteal and endosteal surfaces, the data were digitally filtered, and geometrical properties were computed to include cross-sectional area A, maximum and minimum second moments of area (Imax and Imin), polar second moment of area J, and effective polar second moment of area J(eff). Proportional scaling of geometrical properties with respect to bone length (L2 for A, and L4 for second moments of area) significantly (p < 0.000001) decreased the coefficient of variation in data by an average 36 per cent. From 30-90 per cent distal, J(eff) for the ovine tibia is smaller but within 7 per cent of J--in stark contrast with the human tibia, where J(eff) has been reported as 70-80 per cent of J over the same tibial length. While previous ovine studies involving external fixator pins have employed the same diameter of pin as has been used in humans (that is 5 or 6 mm), a 'first-order' approximation of the data for A, Imax, Imin and J(eff) suggests these pins should be scaled down to 4 mm and 4.75 mm respectively for use on the ovine tibia over the range 25-80 per cent distal along its length.

Sterilization of Fuji pressure-sensitive film.

Fuji Prescale film is a pressure-sensitive medium which produces a characteristic pink stain on the application of pressure. Up to a saturation level, increases in pressure will produce a denser stain, thereby providing a method of determining pressures within the interface between two articulating surfaces. The relationship between the magnitude of applied pressure and the optical density of the resulting stain is non-linear; this relationship also varies with ambient temperature and humidity, in addition to load rate, and therefore requires a calibration procedure prior to use. The use of Fuji prescale film for recording interface pressures within the joint space in vivo has been widely reported; however, the object of this study was to assess the effects of sterilizing this medium, with a view to future in vivo applications. Samples of Fuji film were sterilized using a standard ethylene oxide (ETO) gas process and their subsequent pressure-recording properties were compared to a control group of samples. The 'optical-density vs pressure' relationship for the sterilized group was significantly different from that of the control group (paired Student's t-test, P < = 0.001); however, both groups provided reliable data across the same pressure-range and both exhibited an excellent degree of repeatability (coefficient of variation < 2.5%). It was concluded that Fuji film will continue to produce pressure-stains following ETO sterilization; however, the calibration of this film will only be valid if it is conducted using film from the sterilized group.

The effect of thromboxane A2 receptor antagonism on amphotericin B-induced renal vasoconstriction in the rat.

Amphotericin B (AmB) is the drug of choice for most systemic fungal infections, but doses are frequently reduced because of nephrotoxicity. We investigated the role of thromboxane as a mediator for this nephrotoxicity. Vehicle or amphotericin (0.60 mg/kg) was infused into the left renal artery in four groups of rats, and renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured. Group 1 received vehicle for 90 min. Group 2 received vehicle followed by a 30 minute AmB infusion which caused a significant and reversible fall in the RPF and GFR. Group 3 received vehicle followed by AmB infusion, but were infused with a bolus of ibuprofen (20 mg/kg) 45 minutes before AmB. This group exhibited an insignificant attenuation in the fall in RPF and GFR. Group 4 received vehicle followed by AmB, but were infused with a bolus and continuous infusion of the thromboxane receptor antagonist SQ29,548. This group demonstrated an attenuation in the fall in RPF and a significant decrease in GFR compared to AmB control rats. In addition, the rat glomeruli were incubated with AmB (4 ug/ml). Supernatant levels of thromboxane B2 were significantly elevated in the presence of AmB vs buffer alone. We conclude that the reduction in RPF and GFR observed with AmB infusion in the rat is partially mediated by release of thromboxane.

Effect of cyclooxygenase inhibition on amphotericin B-induced lung injury in awake sheep.

Amphotericin therapy in humans has been reported to cause severe pulmonary dysfunction in some patients, and these abnormalities have been reproduced in unanesthetized sheep. To determine the role of cyclooxygenase products in this response, paired, random-order experiments in 11 sheep were done using the cyclooxygenase inhibitor ibuprofen. Ibuprofen blunted increases in pulmonary artery pressure (Ppa) after amphotericin (peak Ppa 38 +/- 3 cm H2O in amphotericin-alone group vs. 30 +/- 1 cm H2O in ibuprofen + amphotericin group, P less than .05) and reduced peak lung lymph flow to approximately 170% of baseline compared with 350% of baseline in amphotericin-alone group (P less than .05). In addition, the increase in airflow resistance across the lung and the decrease in partial pressure of oxygen seen after amphotericin was blocked by ibuprofen. Therefore, amphotericin-induced lung dysfunction is produced in part through the generation of cyclooxygenase products of arachidonic acid metabolism and can be ameliorated by pretreatment with the cyclooxygenase inhibitor ibuprofen.