Caracterización y asociación clínico bacteriológica en la espondilodiscitis piógena / Bacteriological-clinical association and characterization in Pyogenic Spondylodiscitis

Resumen: Objetivo: Determinar la asociación entre las características clínicas y estudios de laboratorio con el tipo de microorganismo aislado en hemocultivos de pacientes con espondilodiscitis piógena. Material y métodos: Es un estudio transversal analítico, se revisaron expedientes clínicos de pacientes con espondilodiscitis piógena desde Enero de 2013 hasta Enero de 2017. Se realizó análisis descriptivo univariado usando frecuencias y porcentajes para variables cualitativas, medidas de tendencia central y dispersión para las cuantitativas. Análisis bivariado mediante prueba de χ2 o test exacto de Fisher. Análisis de variables cuantitativas mediante t Student o U de Mann-Whitney. Se usó coeficiente de correlación de Spearman. Considerando significancia estadística p < 0.05. Resultados: Se obtuvo una muestra de 34 pacientes, 20 (58%) fueron mujeres, mediana (Me) de edad 60 años (52-66). Se aisló en hemocultivos, bacterias Gram positivas 11 (32.4%) y Gram negativas 23 (67.6%). El microorganismo aislado más frecuente fue Escherichia coli 12 (35.3%). Los pacientes con espondilodiscitis por Gram negativas presentaron dolor leve y velocidad de sedimentación globular (VSG) Me 26 mm/hra P (18-36), los pacientes con espondilodiscitis por Gram positivas presentaron dolor severo y VSG Me 38 mm/h P (34-40) (p = 0.000 y 0.028, respectivamente). La VSG y dolor en el grupo de pacientes con espondilodiscitis por bacterias Gram negativas tuvo un coeficiente de correlación de Spearman moderado 0.418, (p = 0.047); en el grupo de Gram positivas, un coeficiente de correlación de Spearman bajo 0.228, (p = 0.507). Conclusión: Existe una asociación clínica y estadística de manera significativa entre los tipos de microorganismo aislado en hemocultivo, la intensidad del dolor valorado en escala visual análoga (EVA) y los niveles de VSG.

Abstract: Objective: Determine the association between clinical characteristics and laboratory studies with the type of isolated microorganism in blood cultures of patients with Pyogenic Spondylodiscitis. Material and methods: It is a cross-analytical study, clinical records of patients with Pyogenic Spondylodiscitis were reviewed from January 2013 to January 2017. Univariate descriptive analysis was performed using frequencies and percentages for qualitative variables, central trend measures and dispersion for quantitative ones. Bivariate analysis by testing of χ2 or Fisher's exact test. Analysis of quantitative variables using T Student or Mann-Whitney U. Spearman's correlation coefficient was used. Considering statistical significance p < 0.05. Results: A sample of 34 patients was obtained, 20 (58%) were women, median (Me) of age 60 years (52-66). Was isolated into blood cultures, Gram-positive bacteria 11 (32.4%) gram negatives 23 (67.6%). The microorganism most common isolate was Escherichia coli 12 (35.3%). Patients with Gram-negative spondylodiscitis had mild pain and globular sedimentation rate (VSG) Me 26 mm/hra P (18-36), patients with Gram-positive spondylodyscitis had severe pain and VSG Me 38 mm/h P (34-40) (p= 0.000 and 0.028, respectively). VSG and pain in the group of patients with gram-negative bacteria spondylodiscitis had a moderate Spearman correlation coefficient of 0.418, (p = 0.047); in the Gram positives group, a low correlation coefficient of Spearman 0.228, (p = 0.507). Conclusion: There is a clinical and statistical association significant between types of isolated microorganism in blood culture, pain intensity valued on analog visual scale (EVA) and VSG levels.

[Bacteriological-clinical association and characterization in Pyogenic Spondylodiscitis]. / Caracterización y asociación clínico bacteriológica en la espondilodiscitis piógena.

OBJECTIVE: Determine the association between clinical characteristics and laboratory studies with the type of isolated microorganism in blood cultures of patients with Pyogenic Spondylodiscitis. MATERIAL AND METHODS: It is a cross-analytical study, clinical records of patients with Pyogenic Spondylodiscitis were reviewed from January 2013 to January 2017. Univariate descriptive analysis was performed using frequencies and percentages for qualitative variables, central trend measures and dispersion for quantitative ones. Bivariate analysis by testing of 2 or Fishers exact test. Analysis of quantitative variables using T Student or Mann-Whitney U. Spearmans correlation coefficient was used. Considering statistical significance p 0.05. RESULTS: A sample of 34 patients was obtained, 20 (58%) were women, median (Me) of age 60 years (52-66). Was isolated into blood cultures, Gram-positive bacteria 11 (32.4%) gram negatives 23 (67.6%). The microorganism most common isolate was Escherichia coli 12 (35.3%). Patients with Gram-negative spondylodiscitis had mild pain and globular sedimentation rate (VSG) Me 26 mm/hra P (18-36), patients with Gram-positive spondylodyscitis had severe pain and VSG Me 38 mm/h P (34-40) (p= 0.000 and 0.028, respectively). VSG and pain in the group of patients with gram-negative bacteria spondylodiscitis had a moderate Spearman correlation coefficient of 0.418, (p = 0.047); in the Gram positives group, a low correlation coefficient of Spearman 0.228, (p = 0.507). CONCLUSION: There is a clinical and statistical association significant between types of isolated microorganism in blood culture, pain intensity valued on analog visual scale (EVA) and VSG levels.

OBJETIVO: Determinar la asociación entre las características clínicas y estudios de laboratorio con el tipo de microorganismo aislado en hemocultivos de pacientes con espondilodiscitis piógena. MATERIAL Y MÉTODOS: Es un estudio transversal analítico, se revisaron expedientes clínicos de pacientes con espondilodiscitis piógena desde Enero de 2013 hasta Enero de 2017. Se realizó análisis descriptivo univariado usando frecuencias y porcentajes para variables cualitativas, medidas de tendencia central y dispersión para las cuantitativas. Análisis bivariado mediante prueba de 2 o test exacto de Fisher. Análisis de variables cuantitativas mediante t Student o U de Mann-Whitney. Se usó coeficiente de correlación de Spearman. Considerando significancia estadística p 0.05. RESULTADOS: Se obtuvo una muestra de 34 pacientes, 20 (58%) fueron mujeres, mediana (Me) de edad 60 años (52-66). Se aisló en hemocultivos, bacterias Gram positivas 11 (32.4%) y Gram negativas 23 (67.6%). El microorganismo aislado más frecuente fue Escherichia coli 12 (35.3%). Los pacientes con espondilodiscitis por Gram negativas presentaron dolor leve y velocidad de sedimentación globular (VSG) Me 26 mm/hra P (18-36), los pacientes con espondilodiscitis por Gram positivas presentaron dolor severo y VSG Me 38 mm/h P (34-40) (p = 0.000 y 0.028, respectivamente). La VSG y dolor en el grupo de pacientes con espondilodiscitis por bacterias Gram negativas tuvo un coeficiente de correlación de Spearman moderado 0.418, (p = 0.047); en el grupo de Gram positivas, un coeficiente de correlación de Spearman bajo 0.228, (p = 0.507). ­. CONCLUSIÓN: Existe una asociación clínica y estadística de manera significativa entre los tipos de microorganismo aislado en hemocultivo, la intensidad del dolor valorado en escala visual análoga (EVA) y los niveles de VSG.

Utilization of kidneys with similar kidney donor risk index values from standard versus expanded criteria donors.

With the shortage of standard criteria donor (SCD) kidneys, efficient expanded criteria donor (ECD) kidney utilization has become more vital. We investigated the effects of the ECD label on kidney recovery, utilization and outcomes. Using data from the Scientific Registry of Transplant Recipients from November 2002 to May 2010, we determined recovery and transplant rates, and modeled discard risk, for kidneys within a range of kidney donor risk index (KDRI) 1.4-2.1 that included both SCD and ECD kidneys. To further compare similar quality kidneys, these kidneys were again divided into three KDRI intervals. Overall, ECD kidneys had higher recovery rates, but lower transplant rates. However, within each KDRI interval, SCD and ECD kidneys were transplanted at similar rates. Overall, there was increased risk for discard for biopsied kidneys. SCD kidneys in the lower two KDRI intervals had the highest risk of discard if biopsied. Pumped kidneys had a lower risk of discard, which was modulated by KDRI for SCD kidneys but not ECD kidneys. Although overall ECD graft survival was worse than SCD, there were no differences within individual KDRI intervals. Thus, ECD designation adversely affects neither utilization nor outcomes beyond that predicted by KDRI.

Epigenetic and inflammatory marker profiles associated with depression in a community-based epidemiologic sample.

BACKGROUND: Recent work suggests that epigenetic differences may be associated with psychiatric disorders. Here we investigate, in a community-based sample, whether methylation profiles distinguish between individuals with and without lifetime depression. We also investigate the physiologic consequences that may be associated with these profiles. METHOD: Using whole blood-derived genomic DNA from a subset of participants in the Detroit Neighborhood Health Study (DNHS), we applied methylation microarrays to assess genome-wide methylation profiles for over 14 000 genes in 33 persons who reported a lifetime history of depression and 67 non-depressed adults. Bioinformatic functional analyses were performed on the genes uniquely methylated and unmethylated in each group, and inflammatory biomarkers [interleukin (IL)-6 and C-reactive protein (CRP)] were measured to investigate the possible functional significance of the methylation profiles observed. RESULTS: Uniquely unmethylated gene sets distinguished between those with versus without lifetime depression. In particular, some processes (e.g. brain development, tryptophan metabolism) showed patterns suggestive of increased methylation among individuals with depression whereas others (e.g. lipoprotein) showed patterns suggestive of decreased methylation among individuals with depression. IL-6 and CRP levels were elevated among those with lifetime depression and, among those with depression only, IL-6 methylation showed an inverse correlation with circulating IL-6 and CRP. CONCLUSIONS: Genome-wide methylation profiles distinguish individuals with versus without lifetime depression in a community-based setting, and show coordinated signals with pathophysiological mechanisms previously implicated in the etiology of this disorder. Examining epigenetic mechanisms in concert with other dynamic markers of physiologic functioning should improve our understanding of the neurobiology of depression.

Presentation and outcome following radical cystectomy in Hispanics with bladder cancer.

OBJECTIVE: Significant racial and ethnic differences in the epidemiology of bladder cancer (BC) exist. Studies have shown African Americans to have lower incidence of bladder cancer than Caucasians, but higher incidence of invasive BC. Hispanics are the largest minority group in the United States. However, no reported studies on bladder cancer among Hispanics are available to date. As our center is in a unique position to study BC in Hispanic patients we were prompted to assess presentation and outcome of patients undergoing radical cystectomy (RC) for BC. MATERIALS AND METHODS: Between January 1992 and May 2006, 448 RC were performed. All relevant data were collected and entered into a database. Patients were categorized by ethnicity as Hispanic and non-Hispanic White. African-American and other minority groups were excluded because of the small number. Comparative analysis of Hispanic and non-Hispanic White patients was performed. RESULTS: 67 (17%) patients were Hispanic. Mean follow-up period was 41 (SD +/- 40) months. Clinical and pathological data between these two groups were compared. Pre-cystectomy T stage was not significantly different between both groups. However, after RC incidence of < or = T1 disease in Hispanics was lower (22%) than Caucasians (37%). This difference, statistically significant (P = 0.024) indicates that Hispanics who undergo RC present with higher stage disease. Kaplan-Meier log rank test indicated a difference in disease free survival and disease specific survival between the two groups but however it did not reach statistical significance (Log Rank P = 0.082, P = 0.063). No significant difference in overall survival was observed (P = 0.465). CONCLUSIONS: Hispanic patients managed with RC for bladder carcinoma present with higher stage disease.

Downregulation of beta-catenin by human Axin and its association with the APC tumor suppressor, beta-catenin and GSK3 beta.

BACKGROUND: Inactivation of the adenomatous polyposis coli (APC) tumor suppressor protein is responsible for both inherited and sporadic forms of colon cancer. Growth control by APC may relate to its ability to downregulate beta-catenin post-translationally. In cancer, mutations in APC ablate its ability to regulate beta-catenin, and mutations in beta-catenin prevent its downregulation by wild-type APC. Moreover, signaling by the protein product of the wnt-1 proto-oncogene upregulates beta-catenin and promotes tumorigenesis in mice. In a Xenopus developmental system, Wnt-1 signaling was inhibited by Axin, the product of the murine fused gene. This suggests a possible link between Axin, the Wnt-1 signaling components beta-catenin and glycogen synthase kinase 3 beta (GSK3 beta), and APC. RESULTS: Human Axin (hAxin) binds directly to beta-catenin, GSK3 beta, and APC in vitro, and the endogenous proteins are found in a complex in cells. Binding sites for Axin were mapped to a region of APC that is typically deleted due to cancer-associated mutations in the APC gene. Overexpression of hAxin strongly promoted the downregulation of wild-type beta-catenin in colon cancer cells, whereas mutant oncogenic beta-catenin was unaffected. The downregulation was increased by deletion of the APC-binding domain from Axin, suggesting that APC may function to derepress Axin activity. In addition, hAxin dramatically facilitated the phosphorylation of APC and beta-catenin by GSK3 beta in vitro. CONCLUSIONS: Axin acts as a scaffold upon which APC, beta-catenin and GSK3 beta assemble to coordinate the regulation of beta-catenin signaling.

Effects of prolonged controlled mechanical ventilation on diaphragmatic function in healthy adult baboons.

OBJECTIVE: To study diaphragmatic strength and endurance after a prolonged period of mechanical ventilation. DESIGN: Prospective animal study. SETTING: Animal research laboratory. SUBJECTS: Seven uninjured adult baboons (Papio cynocephalus) were anesthetized with ketamine, sedated, paralyzed, and mechanically ventilated. Animals were monitored with pulmonary arterial and peripheral arterial catheters. INTERVENTIONS: Mechanical ventilation was provided for 11 days with an FIO2 of 0.21 and tidal volume of 15 mL/kg. Pulmonary function tests, including lung volumes, arterial blood gases, and chest radiographs were also monitored. Nursing care procedures included frequent turning, chest physiotherapy, and endotracheal suction. Antacids and prophylactic antibiotics (intravenous penicillin, topical polymyxin B, and gentamicin sulfate) were administered. In three animals, fishhook electrodes were surgically placed around both phrenic nerves on both day 0 and after 11 days of mechanical ventilation for diaphragmatic stimulation. On day 0, the electrodes were removed after phrenic nerve stimulation studies were performed. After 11 days of mechanical ventilation, animals were electively killed and full autopsy performed. MEASUREMENTS AND MAIN RESULTS: Hemodynamic and pulmonary function parameters were measured at baseline and every day during the 11 days of mechanical ventilation. Diaphragmatic strength and endurance were measured on days 0 and 11. Diaphragmatic endurance was determined by an inspiratory resistive loading protocol. There were no significant changes in hemodynamics, lung volumes, or gas exchange during the period of mechanical ventilation. On day 7, the chest radiographs showed patchy lobar atelectasis in six animals, which cleared by day 11 in all but two of the animals. Lung pathology showed mild, focal pneumonitis. By day 11, maximum transdiaphragmatic pressure had decreased by 25% from day 0 and diaphragmatic endurance had decreased by 36%. CONCLUSIONS: Eleven days of mechanical ventilation and neuromuscular blockade in healthy baboons resulted in nonsignificant changes in hemodynamics, oxygenation, and/or lung function. However, significant impairment in diaphragmatic endurance and strength were seen. Based on these results, it is likely that prolonged mechanical ventilation by itself impairs diaphragmatic function independent of underlying lung disease.

APEG-1, a novel gene preferentially expressed in aortic smooth muscle cells, is down-regulated by vascular injury.

Despite the importance of phenotypic alterations in arterial smooth muscle cells (ASMC) during the pathogenesis of arteriosclerosis, little is known about genes that define differentiated ASMC. Using differential mRNA display, we isolated a novel gene preferentially expressed in the rat aorta and termed this gene APEG-1. The cDNA of rat APEG-1 contained an open reading frame encoding 113 amino acids, which would predict a basic protein of 12.7 kDa. The amino acid sequence of rat APEG-1 was highly conserved among human and mouse homologues (97 and 98%, respectively). Using an APEG-1 fusion protein containing an N-terminal c-Myc tag, we identified APEG-1 as a nuclear protein. By in situ hybridization, APEG-1 mRNA was expressed in rat ASMC. Although APEG-1 was expressed highly in differentiated ASMC in vivo, its expression was quickly down-regulated and disappeared in dedifferentiated ASMC in culture. In vivo, APEG-1 mRNA levels decreased by more than 80% in response to vascular injury as ASMC changed from a quiescent to a proliferative phenotype. Taken together, these data indicate that APEG-1 is a novel marker for differentiated ASMC and may have a role in regulating growth and differentiation of this cell type.

In situ remineralization of root surface lesions using a fluoride chewing gum or fluoride-releasing device.

The in situ remineralization of early root surface lesions was studied using a fluoride-releasing device (FRD) or a fluoride chewing gum. Root specimens with subsurface lesions were mounted in removable lower appliances in 6 adult subjects. Test groups chewed five sticks/day (0.1 mg F/stick) or one FRD (0.5 mg F/day release rate) was mounted in the midline of the appliance. A fluoride-free dentifrice was used three times/day for each 21-day control and the two test regimens. Separate root lesions were used to measure fluoride uptake or changes in mineral content by quantitative microradiography. Comparable values for percent remineralization for both FRDs and F gum were higher than controls, and the F uptake for FRDs exceeded both the F gum and controls (p = 0.05).

Elastase activity in bronchoalveolar lavage fluid from oxygen-exposed, Pseudomonas-infected baboons.

The adult respiratory distress syndrome is a major cause of morbidity and mortality in critical care patients. Lung injury in this syndrome is frequently associated with lung infection. The combined insults result in an influx of neutrophils and damage to the pulmonary epithelium. We investigated whether active neutrophil elastolytic activity was present in the bronchoalveolar fluid in baboons with mild or moderate hyperoxic lung injury and infection. Group A (N = 7) was exposed for 6 days to FIO2 = 0.8 and then inoculated by intratracheal bolus with Pseudomonas aeruginosa strain DGI-R130 (PA); the FIO2 was reduced to 0.5. Group B (N = 6) was exposed to similar concentrations of inspired oxygen but inoculated with buffered saline. Antibiotics included parenteral penicillin and topical gentamicin and polymyxin B. All 3 were given continuously in group B but stopped 24 h prior to PA inoculation in group A. Bronchoalveolar lavage fluid was collected 1 week before oxygen administration, when the FIO2 was reduced (day 6 or 7) and prior to necropsy (day 11). Hemodynamic, pulmonary function, microbiological, and biochemical variables were studied. Injured, infected animals (group A) had significant elevations of mean pulmonary artery pressure and decreases in total lung capacity and PaO2 compared both to baseline and to group B at day 11. At autopsy, group A had significant increases of bronchoalveolar lavage fluid (BALF) neutrophils and bacterial pathogens. Elastase levels in BALF (equal to 0 at baseline) rose to 136 +/- 98 ng/ml in group A vs. 6 +/- 14 ng/ml in group B. The elastase was inhibited by inhibitors of serine proteases including ones specific for neutrophil elastase. On Sephacryl S-300 chromatography the elastase activity eluted near human alpha 2-macroglobulin and separated from other proteolytic activity. These studies demonstrate a significant level of elastase in BALF from injured, infected baboons compared to injured, uninfected animals.

Bacteriologic diagnosis of nosocomial pneumonia following prolonged mechanical ventilation.

Cultures of tracheal secretions, bronchoalveolar lavage (BAL), protected specimen brushes (PSB), and direct lung aspirates were compared with cultures of lung homogenates and histologic findings in 35 baboons after 7 to 10 days of intubation and mechanical ventilation. Six animals received no antibiotics, while the remainder were treated with a variety of prophylactic regimens of intravenous and topical agents. Bacterial contamination at each culture site was expressed as a "bacterial index" (BI), obtained as the sum of the logarithmic concentrations of individual species. In the absence of antibiotics, pneumonias occurred in all animals and were polymicrobial; 56% of organisms in lung tissue were members of the normal upper respiratory tract flora, while 44% were gram-negative bacilli with a mean total bacterial index of 13.94/g. Lobar tissue BI values greater than 6.0/g were found in 77% of lobes containing pneumonias judged by histologic criteria to be moderate or severe in extent, whereas only 7% of lobes with lesser inflammatory changes had similar BI values. The BI values of BAL were linearly related to tissue values, whether the BAL was performed of the same lobe cultured or a different lobe. BAL recovered 74% of all species present in lung tissue compared to 41% by PSB and 56% for needle aspirates. False positive specimens were found with similar frequency with these 3 procedures. Tracheal aspirates revealed 78% of organisms found in lung tissue, but 14 of 35 (40%) of species isolated were not present in lung tissue. BAL provides the best reflection of the lung's bacterial burden, both quantitatively and qualitatively, in the setting of prolonged intubation and ventilation.

Prevention of nosocomial pneumonia using topical and parenteral antimicrobial agents.

The efficacy of antimicrobial agents applied topically in the oropharynx and trachea with and without intravenous antibiotics in preventing bacterial pneumonias during prolonged (7 to 10 days) mechanical ventilation was studied in 35 baboons, 30 of which had acute lung injury induced by either oleic acid or hyperoxia. In 12 animals receiving no antibiotics, only topical application of polymyxin B (PB), or only intravenous penicillin and gentamicin (IV PCN/GM), moderate or severe pneumonia was found in 81% of lobes examined at necropsy; no lobes were sterile. Pneumonias were polymicrobial in the absence of antibiotics, due to PCN-sensitive organisms in the topical PB group, and due to gram-negative bacilli in the IV PCN/GM group. Combinations of topical PB or GM or both plus IV PCN were highly efficacious in preventing pneumonia in 23 animals as only 15% of the lobes contained moderate to severe pneumonia and 52% of lobes were sterile. In these groups, histologically evident pneumonias were associated with low concentrations of bacteria in lung tissue, principally gram-negative bacilli resistant to the topical agent being used. Resistance to PB appeared to be solely due to selection of intrinsically resistant species, whereas resistance to GM may have developed through additional mechanisms as well. Although this approach to pneumonia prevention is clearly efficacious in this animal model, clinical studies are needed to define the frequency and significance of microbial resistance in human subjects.

One hundred percent oxygen lung injury in adult baboons.

Healthy adult baboons exposed to 100% oxygen for 5 to 7 days maintained on continuous mechanical ventilation develop severe bilateral noncardiogenic pulmonary edema that resembles in many aspects the human adult respiratory distress syndrome (ARDS). In the present study, we evaluated the effects of hyperoxia for 5 to 6 days in 8 baboons to compare changes in abnormalities in bronchoalveolar lavage fluid (BALF) biochemical markers, hemodynamic measurements, and pulmonary function tests in order to find early predictors of lung injury. All animals had bilateral alveolar infiltrates, severe hypoxemia, and progressive deterioration of pulmonary function tests. Diffuse alveolar damage and mild-moderate pneumonias were found and were associated with low-grade bacterial infection. Total lung capacity, diffusing capacity for carbon monoxide, pulmonary static compliance, and oxygenation were significantly impaired after Day 5; BALF proteins, elastase, and total polymorphonuclear leukocytes increased significantly at least 24 h before (Day 4) any abnormalities in chest radiographs, pulmonary function tests, and hemodynamic measurements were detected. We conclude that exposure to 100% oxygen in this model causes marked gas exchange, hemodynamic, biochemical, cytologic, radiographic, and pathologic changes similar to those noted in patients with ARDS. Bronchoalveolar lavage abnormalities precede hemodynamic and gas exchange abnormalities.

Near-triploid Ph-positive leukemia.

Tetraploid populations have been observed in various types of leukemia, but relatively few reports exist of triploid cell populations in acute or chronic leukemia. We report two cases of Ph-positive leukemia with a modal triploid cell population. Examination of peripheral blood from a 3-year-old boy with Ph-positive acute lymphoblastic leukemia (ALL) and a 68-year-old male with Ph-positive chronic myelocytic leukemia (CML) in blastic crisis revealed modal populations of 72 and 63 chromosomes, respectively. G-banding analysis of both cases revealed the following: karyotypic instability (no clonality), dominant trisomy, and the random association of the Ph chromosome with gains and losses of chromosomes involved in this translocation. The cytogenetic evidence obtained suggests that the triploid cell populations were not derived from a duplication of a hypodiploid cell population, but resulted from random loss of chromosomes from tetraploid cell populations derived from duplication of pseudodiploid cells.

Hyperoxia exposure in mechanically ventilated primates with and without previous lung injury.

The response of the injured lung to hyperoxia is uncertain. In the present study, we evaluated the effects of 100% oxygen exposure for 120-168 h in mechanically ventilated baboons with or without previous diffuse alveolar damage (DAD) induced by oleic acid. These two groups were compared with another group of six baboons previously studied in our laboratory in which DAD induced with oleic acid was followed by ventilation with 40% oxygen. Oleic acid infusion caused a prompt reduction in total lung capacity, static compliance, and diffusion capacity and an increase in lung tissue volume. The magnitude and course of oleic acid lung injury was similar for 4 days in animals breathing 100% or 40% O2. Animals breathing 100% O2 without previous lung injury developed significant decreases in total lung capacity, oxygenation, and diffusion capacity after 72 h of hyperoxia. By 120 h, lung function was similarly impaired in both 100% O2-breathing groups, and rapidly worsening pulmonary edema appeared radiographically between 5.5 and 7 days in all O2-exposed animals. Subsequent weaning was successful in only three animals after 100% O2 exposure. All but one animal in the 40% O2 group were easily weaned. Histologic changes between 6 and 14 days in 100% O2 animals showed a marked proliferative response, particularly of type 2 cells; no differences were found due to prior oleic acid injury. Resolution of this process occurred in a surviving animal, resulting in focal fibrotic residua at 6 weeks, similar to that observed in 40% O2 oleic acid-treated survivors. Previous lung injury due to oleic acid did not modify the response of the baboon lung to hyperoxia.

Adjuvant chemotherapy in advanced head and neck cancer. An update.

Two courses of triple-agent chemotherapy were given to 47 patients with advanced head and neck cancer. All but one patient with a nasopharyngeal carcinoma had resectable stage III and IV squamous cell carcinoma. Eighty-eight percent of the patients responded to the chemotherapy with a 50 percent or greater decrease in tumor size. Forty-three patients underwent surgical resection and 19 were histologically upgraded to stage II or better (T less than 2 cm, N0). None of these 19 patients have relapsed, with follow-up ranging from 12 to 42 months. In 12 of the 47 patients, recurrent tumor developed within the first 18 months of follow-up.

Hypothalamic cuts suggest a brain site for the antigonadotrophic action of melatonin in the Syrian hamster.

Thrice daily melatonin injections inhibit reproductive functions in pinealectomized male hamsters, as measured by sex organ weights and plasma testosterone levels. Total or anterior, but not posterior, hypothalamic deafferentation prevented the antigonadotrophic effect of melatonin. The findings suggest a site of action of melatonin within the central nervous system.