GLUT4 heterozygous knockout mice develop muscle insulin resistance and diabetes.

GLUT4, the insulin-responsive glucose transporter, plays an important role in postprandial glucose disposal. Altered GLUT4 activity is suggested to be one of the factors responsible for decreased glucose uptake in muscle and adipose tissue in obesity and diabetes. To assess the effect of GLUT4 expression on whole-body glucose homeostasis, we disrupted the murine GLUT4 gene by homologous recombination. Male mice heterozygous for the mutation (GLUT4 +/-) exhibited a decrease in GLUT4 expression in adipose tissue and skeletal muscle. This decrease in GLUT4 expression did not result in obesity but led to increased serum glucose and insulin, reduced muscle glucose uptake, hypertension, and diabetic histopathologies in the heart and liver similar to those of humans with non-insulin-dependent diabetes mellitus (NIDDM). The male GLUT4 +/- mice represent a good model for studying the development of NIDDM without the complications associated with obesity.

Distribution of lysosome-associated membrane proteins-1 and -2, and cathepsin D in eosinophilic granular bodies: possible relationship to cyst development in pilocytic astrocytomas.

Pilocytic astrocytomas are usually cystic; cyst formation within these tumours may result in increased intracranial pressure, due to the effect of their mass, and contribute to cerebral damage. Eosinophilic granular bodies (EGBs) are produced abundantly in pilocytic astrocytomas but their role in disease progression remains unknown. Immunohistochemistry studies showed EGBs to exhibit pronounced reactivity to antibodies against lysosome-associated membrane proteins (LAMP)-1 and LAMP-2, and the lysosomal enzyme cathepsin D. Both LAMP-1 and LAMP-2 showed peripheral rim and granular staining patterns. The EGBs were scattered widely across cysts and, where EGBs aggregated in clusters, were usually close to areas of fluid in the cysts. Most EGBs had nuclei either attached or close by, indicating that the EGBs may be derived from anucleated astrocytes. The results suggest that EGBs, together with other factors, may play a role in the development of cysts in pilocytic astrocytomas.

Seasonal variation of chemical characteristics of fine particulate matter at a high-elevation subtropical forest in East Asia.

The aim of this study was to chemically characterize the fine particulate matter (PM2.5) at a subtropical forest in East Asia under the influences of anthropogenic and biogenic sources and a complex topographic setting. Four seasonal campaigns were conducted at the Xitou Experimental Forest in central Taiwan from the winter of 2013 to the autumn of 2014. The results indicated that the ambient levels and chemical features of PM2.5 exhibited pronounced seasonal variations. Non-sea-salt sulfate (nss-SO42-) constituted the major component of PM2.5, followed by ammonium (NH4+) and nitrate (NO3-) during winter, summer and autumn. However, it was revealed that the mass fraction of NO3- increased to be comparable with that of nss-SO42- in springtime. The mass contribution of secondary organic carbon (SOC) to PM2.5 peaked in summer (13.2%), inferring the importance of enhanced photo-oxidation reactions in SOC formation. Diurnal variations of O3 and SO2 coincided with each other, suggesting the transport of aged pollutants from distant sources, whereas CO and NOx were shown to be under the influences of both local and regional sources. Notably high sulfur oxidation ratio (SOR) and nitrogen oxidation ratio (NOR) were observed, which were 0.93 ±â€¯0.05 and 0.39 ±â€¯0.20, respectively. Precursor gases (i.e. SO2 and NOx) could be converted to sulfate and nitrate during the transport by the uphill winds. Furthermore, due to the high relative humidity at Xitou, enhanced aqueous-phase and/or heterogeneous reactions could further contribute to the formation of sulfate and nitrate at the site. This study demonstrated the significant transport of urban pollutants to a subtropical forest by the mountain-valley circulations as well as the long-range transport from regional sources, whereas the implications of which for regional climate change necessitated further investigation.

Impaired JAK-STAT signal transduction contributes to growth hormone resistance in chronic uremia.

Chronic renal failure (CRF) is associated with resistance to the growth-promoting and anabolic actions of growth hormone (GH). In rats with CRF induced by partial renal ablation, 7 days of GH treatment had a diminished effect on weight gain and hepatic IGF-1 and IGFBP-1 mRNA levels, compared with sham-operated pair-fed controls. To assess whether GH resistance might be due to altered signal transduction, activation of the JAK-STAT pathway was studied 10 or 15 minutes after intravenous injection of 5 mg/kg GH or vehicle. Hepatic GH receptor (GHR) mRNA levels were significantly decreased in CRF, but GHR protein abundance and GH binding to microsomal and plasma membranes was unaltered. JAK2, STAT1, STAT3, and STAT5 protein abundance was also unchanged. However, GH-induced tyrosine phosphorylation of JAK2, STAT5, and STAT3 was 75% lower in the CRF animals. Phosphorylated STAT5 and STAT3 were also diminished in nuclear extracts. The expression of the suppressor of cytokine signaling-2 (SOCS-2) was increased twofold in GH-treated CRF animals, and SOCS-3 mRNA levels were elevated by 60% in CRF, independent of GH treatment. In conclusion, CRF causes a postreceptor defect in GH signal transduction characterized by impaired phosphorylation and nuclear translocation of GH-activated STAT proteins, which is possibly mediated, at least in part, by overexpression of SOCS proteins.

Muscle-specific transgenic complementation of GLUT4-deficient mice. Effects on glucose but not lipid metabolism.

We have taken the approach of introducing the muscle-specific myosin light chain (MLC)-GLUT4 transgene into the GLUT4-null background to assess the relative role of muscle and adipose tissue GLUT4 in the etiology of the GLUT4-null phenotype. The resulting MLC-GLUT4-null mice express GLUT4 predominantly in the fast-twitch extensor digitorum longus (EDL) muscle. GLUT4 is nearly absent in female white adipose tissue (WAT) and slow-twitch soleus muscle of both sexes of MLC-GLUT4-null mice. GLUT4 content in male MLC-GLUT4-null WAT is 20% of that in control mice. In transgenically complemented EDL muscle, 2-deoxyglucose (2-DOG) uptake was restored to normal (male) or above normal (female) levels. In contrast, 2-DOG uptake in slow-twitch soleus muscle of MLC-GLUT4-null mice was not normalized. With the normalization of glucose uptake in fast-twitch skeletal muscle, whole body insulin action was restored in MLC-GLUT4-null mice, as shown by the results of the insulin tolerance test. These results demonstrate that skeletal muscle GLUT4 is a major regulator of skeletal muscle and whole body glucose metabolism. Despite normal skeletal muscle glucose uptake and insulin action, the MLC-GLUT4-null mice exhibited decreased adipose tissue deposits, adipocyte size, and fed plasma FFA levels that are characteristic of GLUT4-null mice. Together these results indicate that the defects in skeletal muscle and whole body glucose metabolism and adipose tissue in GLUT4-null mice arise independently.

Diverse effects of Glut 4 ablation on glucose uptake and glycogen synthesis in red and white skeletal muscle.

The ability of muscles from Glut 4-null mice to take up and metabolize glucose has been studied in the isolated white EDL and red soleus muscles. In EDL muscles from male or female Glut 4-null mice, basal deoxyglucose uptake was lower than in control muscles and was not stimulated by insulin. In parallel, glycogen synthesis and content were decreased. Soleus muscles from male Glut 4-null mice took up twice more deoxyglucose in the absence of insulin than control muscles, but did not respond to insulin. In females, soleus deoxyglucose uptake measured in the absence of hormone was similar in Glut 4-null mice and in control mice. This uptake was stimulated twofold in Glut 4-null mice and threefold in control mice. Basal glycogen synthesis was increased by 4- and 2.2-fold in male and female null mice, respectively, compared to controls, and insulin had no or small (20% stimulation over basal) effect. These results indicate that while EDL muscles behaved as expected, soleus muscles were able to take up a large amount of glucose in the absence (males) or the presence of insulin (females). Whether this is due to a change in Glut 1 intrinsic activity or targeting and/or to the appearance of another glucose transporter remains to be determined.

PRP19: a novel spliceosomal component.

We have isolated the gene of a splicing factor, PRP19, by complementation of the temperature-sensitive growth defect of the prp19 mutant of Saccharomyces cerevisiae. The gene encodes a protein of 502 amino acid residues of molecular weight 56,500, with no homology to sequences in the data base. Unlike other PRP proteins or mammalian splicing factors, the sequence of PRP19 has no discernible motif. Immunoprecipitation studies showed that PRP19 is associated with the spliceosome during the splicing reaction. Although the exact function of PRP19 remains unknown, PRP19 appears to be distinct from the other PRP proteins or other spliceosomal components.

Construction of a defective retrovirus containing the human hypoxanthine phosphoribosyltransferase cDNA and its expression in cultured cells and mouse bone marrow.

Defective ecotropic and amphotropic retroviral vectors containing the cDNA for human hypoxanthine phosphoribosyltransferase (HPRT) were developed for efficient gene transfer and high-level cellular expression of HPRT. Helper cell clones which produced a high viral titer were generated by a simplified method which minimizes cell culture. We used the pZIP-NeoSV(X) vector containing a human hprt cDNA. Viral titers (1 X 10(3) to 5 X 10(4)/ml) of defective SVX HPRT B, a vector containing both the hprt and neo genes, were increased 3- to 10-fold by cocultivation of the ecotropic psi 2 and amphotropic PA-12 helper cells. Higher viral titers (8 X 10(5) to 7.5 X 10(6] were obtained when nonproducer NIH 3T3 cells or psi 2 cells carrying a single copy of SVX HPRT B were either transfected or infected by Moloney leukemia virus. The SVX HPRT B defective virus partially corrected the HPRT deficiency (4 to 56% of normal) of cultured rodent and human Lesch-Nyhan cells. However, instability of HPRT expression was detected in several infected clones. In these unstable variants, both retention and loss of the SVX HPRT B sequences were observed. In the former category, cells which became HPRT- (6-thioguanine resistant [6TGr]) also became G418s, indicative of a cis-acting down regulation of expression. Both hypoxanthine-aminopterin-thymidine resistance (HATr) and G418r could be regained by counterselection in hypoxanthine-aminopterin-thymidine. In vitro mouse bone marrow experiments indicated low-level expression of the neo gene in in vitro CFU assays. Individual CFU were isolated and pooled, and the human hprt gene was shown to be expressed. These studies demonstrated the applicability of vectors like SVX HPRT B for high-titer production of defective retroviruses required for hematopoietic gene transfer and expression.

Snt309p, a component of the Prp19p-associated complex that interacts with Prp19p and associates with the spliceosome simultaneously with or immediately after dissociation of U4 in the same manner as Prp19p.

The yeast protein Prp19p is essential for pre-mRNA splicing and is associated with the spliceosome concurrently with or just after dissociation of U4 small nuclear RNA. In splicing extracts, Prp19p is associated with several other proteins in a large protein complex of unknown function, but at least one of these proteins is also essential for splicing (W.-Y. Tarn, C.-H. Hsu, K.-T. Huang, H.-R. Chen, H.-Y. Kao, K.-R. Lee, and S.-C. Cheng, EMBO J. 13:2421-2431, 1994). To identify proteins in the Prp19p-associated complex, we have isolated trans-acting mutations that exacerbate the phenotypes of conditional alleles of prp19, using the ade2-ade3 sectoring system. A novel splicing factor, Snt309p, was identified through such a screen. Although the SNT309 gene was not essential for growth of Saccharomyces cerevisiae under normal conditions, yeast cells containing a null allele of the SNT309 gene were temperature sensitive and accumulated pre-mRNA at the nonpermissive temperature. Far-Western blot analysis revealed direct interaction between Prp19p and Snt309p. Snt309p was shown to be a component of the Prp19p-associated complex by Western blot analysis. Immunoprecipitation studies demonstrated that Snt309p was also a spliceosomal component and associated with the spliceosome in the same manner as Prp19p during spliceosome assembly. These results suggest that the functions of Prp19p and Snt309p in splicing may require coordinate action of these two proteins.

Altered hepatic and muscle substrate utilization provoked by GLUT4 ablation.

Studies were conducted to explore altered substrate utilization and metabolism in GLUT4 null mice. Liver fatty acid synthase mRNA and fatty acid synthesis rates were dramatically increased in GLUT4 null mice compared with control mice and were supported by increased rates of the pentose phosphate pathway oxidative phase and sterol regulatory binding protein mRNA expression. Increased GLUT2 protein content, glucokinase mRNA, and glucose-6-phosphate in GLUT4 null mice may provide substrate for the enhanced fatty acid synthesis. Increased fatty acid synthesis, however, did not lead to hepatic triglyceride accumulation in GLUT4 null mice because of increased hepatic triglyceride secretion rates. GLUT4 null mice rapidly cleared orally administered olive oil, had reduced serum triglyceride concentrations in the fed and the fasted state, and increased skeletal muscle lipoprotein lipase when compared with controls. Oleate oxidation rates were increased in GLUT4 null skeletal muscle in association with mitochondrial hyperplasia/hypertrophy. This study demonstrated that GLUT4 null mice had increased hepatic glucose uptake and conversion into triglyceride for subsequent use by muscle. The ability of GLUT4 null mice to alter hepatic carbohydrate and lipid metabolism to provide proper nutrients for peripheral tissues may explain (in part) their ability to resist diabetes when fed a normal diet.

Effects on mouse blastocysts of in vitro exposure to methylnitrosourea and 3-methylcholanthrene.

Mouse blastocysts were exposed in vitro to various concentrations of N-methyl-N-nitrosourea and 3-methylcholanthrene. The incorporation of [3H]thymidine, [3H]uridine, and [3H]leucine into the exposed blastocysts was determined either immediately following exposure or after 18 hr of culture. The concentrations of N-methyl-N-nitrosourea or 3-methylcholanthrene used had no effect on blastocyst viability in either situation. There was a concentration-dependent decrease in the incorporation of the precursors into blastocysts exposed to N-methyl-N-nitrosourea which appears to be more pronounced after 18 hr in culture. This effect was not demonstrated for 3-methylcholanthrene, which requires metabolic activation for reactivity. Blastocysts exposed to N-methyl-N-nitrosourea were injected into the uterine horns of surrogate mothers; a significant increase in the resorption rate of these blastocysts was seen when compared with controls. Similar experiments were performed to determine birth rate. A dose-dependent decrease in birth rate was observed which correlated well with the effects on incorporation of thymidine, uridine, and leucine but not with the effect of implantation rate.

Prevention of insulin resistance and diabetes in mice heterozygous for GLUT4 ablation by transgenic complementation of GLUT4 in skeletal muscle.

Impaired skeletal muscle glucose utilization under insulin action is a major defect in the etiology of type 2 diabetes. This is underscored by a new mouse model of type 2 diabetes generated by genetic disruption of one allele of glucose transporter 4 (GLUT4+/-), the insulin-responsive glucose transporter in muscle and adipose tissue. Male GLUT4+/- mice exhibited decreased GLUT4 expression and glucose uptake in muscle that accompanied impaired whole-body glucose utilization, hyperinsulinemia, hyperglycemia, and heart histopathology. To determine whether development of the diabetic phenotype in GLUT4+/- mice can be forestalled by preventing the onset of impaired muscle GLUT4 expression and glucose utilization, standard genetic crossing was performed to introduce a fast-twitch muscle-specific GLUT4 transgene--the myosin light chain (MLC) promoter-driven transgene MLC-GLUT4--into GLUT4+/- mice (MLC-GLUT4+/- mice). GLUT4 expression and 2-deoxyglucose uptake levels were normalized in fast-twitch muscles of MLC-GLUT4+/- mice. In contrast to GLUT4+/- mice, MLC-GLUT4+/- mice exhibited normal whole-body glucose utilization. In addition, development of hyperinsulinemia and hyperglycemia observed in GLUT4+/- mice was prevented in MLC-GLUT4+/- mice. The occurrence of diabetic heart histopathology in MLC-GLUT4+/- mice was reduced to control levels. Based on these results, we propose that the onset of a diabetic phenotype in GLUT4+/- mice can be avoided by preventing decreases in muscle GLUT4 expression and glucose uptake.

Enhanced insulin action due to targeted GLUT4 overexpression exclusively in muscle.

Dysregulation of GLUT4, the insulin-responsive glucose transporter, is associated with insulin resistance in skeletal muscle. Although skeletal muscle is the major target of insulin action, muscle GLUT4 has not been linked causally to whole-body insulin sensitivity and regulation of glucose homeostasis. To address this, we generated a line of transgenic mice that overexpresses GLUT4 in skeletal muscle. We demonstrate that restricted overexpression of GLUT4 in fast-twitch skeletal muscles of myosin light chain (MLC)-GLUT4 transgenic mice induces a 2.5-fold increase in insulin-stimulated 2-deoxyglucose uptake in transgene-overexpressing cells. Consequently, glycogen content is increased in the fast-twitch skeletal muscles under insulin action (5.75 +/- 1.02 vs. 3.24 +/- 0.26 mg/g). This indicates that insulin-stimulated glucose transport is partly rate-limiting for glycogen synthesis. At the whole-body level, insulin-stimulated glucose turnover is increased 2.5-fold in unconscious MLC-GLUT4 mice. Plasma glucose and insulin levels in MLC-GLUT4 mice are altered as a result of increased insulin action. In 2- to 3-month-old MLC-GLUT4 mice, fasting insulin levels are decreased (0.43 +/- 0.05 vs. 0.74 +/- 0.10 microgram/l), whereas normal fasting glycemia is maintained. Conversely, 7- to 9-month-old MLC-GLUT4 mice exhibit decreased fasting glycemia (5.75 +/- 0.73 vs. 8.11 +/- 0.57 mmol/l) with normal insulin levels. Fasting plasma lactate levels are elevated in both age groups (50-100%). Additionally lipid metabolism is affected by skeletal muscle GLUT4 overexpression. This is indicated by changes in plasma free fatty acid and beta-hydroxybutyrate levels. These studies underscore the importance of GLUT4 in the regulation of glucose homeostasis and its interaction with lipid metabolism.

Effect of bacitracin on retroendocytosis and degradation of insulin in cultured kidney epithelial cell line.

In an earlier study, we described the presence of a retroendocytotic pathway for insulin in a cultured kidney epithelial cell line. Derived from the opossum kidney (OK), these cells possess many features of proximal tubule epithelium, which is the major site of kidney insulin metabolism. We studied the interaction between the retroendocytotic and the degradative pathways with bacitracin as a pharmacological probe. Monolayers of OK cells were loaded with 125I-labeled insulin over 30 min, acid washed to remove membrane-bound insulin, then incubated in fresh medium for 60 min while the release of intracellular radioactivity was monitored. In experiments carried out in the presence of bacitracin (2 mM), there was a two-thirds increase in intracellular radioactivity at the end of the loading phase. Measurements made during the subsequent release phase showed that bacitracin reduced the release of degradation products. Thus, although controls released 72.1 +/- 8.1% of the internalized radioactivity as trichloroacetic acid (TCA)-soluble products, bacitracin-treated cells released 59.2 +/- 9.4% (P less than 0.02). In contrast, release of TCA-precipitable insulin increased from 15.2 +/- 4.6% in controls to 25.8 +/- 3.7% in bacitracin-treated cells (P less than 0.01). In separate experiments analyzed by gel-exclusion chromatography, 6.4 +/- 0.6% of radioactivity released from preloaded control cells into medium over 60 min was insulin sized compared to 29.7 +/- 1.4% in bacitracin-treated cells. High-performance liquid chromatography revealed that 61.5 +/- 3.5% of this insulin-sized material released from control cells preloaded with A14-insulin eluted as intact insulin and the remainder as unidentified intermediate degradation products.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation and targeting of antiapoptotic XIAP in acute myeloid leukemia.

XIAP is a member of the inhibitors-of-apoptosis family of proteins, which inhibit caspases and block cell death, with prognostic importance in AML. Here we demonstrate that cytokines regulate the expression of XIAP in leukemic cell lines and primary AML blasts. Inhibition of phosphatidylinositol-3 kinase (PI3K) with LY294002 and of the mitogen-activated protein kinase (MAPK) cascade by PD98059 resulted in decreased XIAP levels (34+/-8.7 and 23+/-5.7%, respectively). We then generated OCI-AML3 cells with constitutively phosphorylated Akt (p473-Akt) by retroviral gene transfer. Neither these nor Akt inhibitor-treated OCI-AML3 cells showed changes in XIAP levels, suggesting that XIAP expression is regulated by PI3K downstream effectors other than Akt. The induction of XIAP expression by cytokines through PI3K/MAPK pathways is consistent with its role in cell survival. Exposure of leukemic cells to chemotherapeutic agents decreased XIAP protein levels by caspase-dependent XIAP cleavage. Targeting XIAP by XIAP antisense oligonucleotide resulted in downregulation of XIAP, activation of caspases and cell death, and sensitized HL-60 cells to Ara-C. Our results suggest that XIAP is regulated by cytokines through PI3K, and to a lesser degree through MAPK pathways. Selective downregulation of XIAP expression might be of therapeutic benefit to leukemic patients.

The metabolic consequences of altered glucose transporter expression in transgenic mice.

Glucose transporters are a family of membrane proteins which mediate glucose uptake across the cell membrane. The facilitative glucose transporter proteins are products of unique genes and are expressed in a tissue-specific manner. They are very similar structurally, containing 12 putative membrane spanning domains. Functionally they vary in their affinity for glucose and sensitivity to hormones such as insulin. Glucose homeostasis depends mainly on controlled changes in glucose transport in insulin-responsive tissues such as skeletal muscle and adipose cells where both glucose transporter 1 and glucose transporter 4 are expressed. Glucose transporter 4 is the major glucose transporter in these tissues and translocates from an intracellular vesicle to the cell membrane in response to insulin. Alterations of the level of expression of these glucose transporters should result in changes in insulin sensitivity and modification of whole-body metabolism. To test these hypotheses transgenic mouse models have been generated which overexpress glucose transporters in specific tissues or in the whole body. Glucose transporter 1 and glucose transporter 4 have been overexpressed specifically in skeletal muscle and glucose transporter 4 specifically in adipose tissue. Mice have also been made which overexpress glucose transporter 4 in the whole body. Using homologous recombination technology to disrupt the glucose transporter 4 gene, a "knockout" mouse has been created which expresses no glucose transporter 4. The metabolic consequences of these genetic manipulations on the level of expression of glucose transporters in the mouse are reviewed. The future applications of transgenic mouse technology in creating models which mimic human diseases are also discussed.

In vitro accommodation of immortalized porcine endothelial cells: resistance to complement mediated lysis and down-regulation of VCAM expression induced by low concentrations of polyclonal human IgG antipig antibodies.

The capacity of vascularized xenografts to survive in the face of normal levels of circulating antigraft antibodies and complement has been ascribed to a phenomenon referred to as "endothelial cell accommodation." The mechanisms whereby accommodation might occur have remained obscure. We have investigated this phenomenon in an in vitro system. A preparation of polyclonal immunoglobulin, human normal globulin (HNG), induced a change in the phenotype of immortalized porcine endothelial cells (IPEC) suggestive of accommodation; the cells became resistant to complement mediated lysis and displayed a reduced expression of surface VCAM and MHC class I. The accommodated phenotype only manifested after 72 hr incubation with HNG and was optimal after 120 hr. In an analysis of all the experiments performed, the development of resistance to complement mediated lysis appeared independent of the inducing dose of HNG. However, down-regulation of VCAM was only manifest when subsaturating doses were used. Our results suggest that IgG xenoreactive antibodies can mediate changes in porcine endothelial cell phenotype consistent with accommodation. The dependence on both time and dose of antibody applied might explain why accommodation has been difficult to achieve consistently in in vivo models of discordant xenotransplantation. By demonstrating a functional interaction between human VLA-4 and porcine VCAM, we speculate that the down-regulation in expression of VCAM on accommodated endothelium may have an important regulatory effect on traffic of inflammatory cells into xenografts. Our results have important implications for the development of strategies to promote accommodation of xenografts.

Whole lung tuberculosis. A disease with high mortality which is frequently misdiagnosed.

The mortality rate of WLTB was significantly higher than non-WLTB in 45 of 516 cases of PTB in a 24-month period. There is no known underlying disease predisposing to WLTB. Clinically, the patients were significantly more toxic and had lower serum albumin and hemoglobin levels than non-WLTB patients. They had a lower rate of positive PPD tuberculin skin tests. The chest roentgenograms revealed three patterns: (1) DBS type in 15--all with multiple or diffuse opacities with or without cavitations; (2) DHS type in 20--eight with typical miliary lesions and 12 with atypical miliary patterns; (3) combined focal PTB and DHS type in ten. We found that atypical chest roentgenographic patterns were common in WLTB and frequently led to misdiagnosis. The delayed diagnosis and treatment of this advanced disease resulted in the high mortality. Early, empirical antituberculosis chemotherapy is indicated and life-saving.

Pulmonary manifestations of Staphylococcus aureus septicemia.

This study includes 140 episodes (138 cases) of Staphylococcus aureus septicemia, made up mostly of community-acquired, nonintravenous drug abuse (nonIVDA) cases. Unlike other series, injury wounds and skin or soft tissue infections were the most common sites of primary infection. In spite of a different patient population and lack of cases with tricuspid valvular endocarditis, the lungs were still the most common site of secondary infectious foci and most developed within two weeks of onset of the septicemia.

Treatment for collapsed lung in critically ill patients. Selective intrabronchial air insufflation using the fiberoptic bronchoscope.

A new, simpler method to re-expand collapsed lungs was introduced in 14 procedures in 12 critically ill patients. To close the bronchus, we wedge the fiberoptic bronchoscope into each segment or subsegment of the collapsed lung instead of using a balloon cuff. Room air was then insufflated into the atelectatic alveoli after repetitive sputum suctioning and bronchial washing with normal saline solution. Complete re-expansion was achieved in 12 of the 14 procedures and partial in two. The average alveolar-arterial oxygen pressure difference (P[A-a]O2) declined from 217.5 before the procedure to 200.3, 150.0 and 152.2, respectively at 30 minutes, 12 hours and 24 hours after. There were no complications.