Current and future approaches to large airways imaging in adults and children.

"Large airways disease" is a catch-all phrase encompassing a wide variety of pathology affecting the trachea, main, lobar, segmental, and proximal sub-segmental bronchi. Relevant pathologies can be divided into focal or diffuse processes and many conditions have classic appearances on computed tomography (CT). We provide a review of the imaging specifics of a wide range of large airway pathologies in adult, childhood, and fetal life with examples of common and rare pathologies ranging from well-known entities such as cystic fibrosis and allergic bronchopulmonary aspergillosis to rarities such as Williams-Campbell, primary ciliary dyskinesia, and congenital high-airway obstruction syndrome (CHAOS). Although the spatial and temporal resolution of modern multidetector CT lends itself well to the depiction of small structures such as the peripheral airways, concerns regarding radiation exposure and increasing interest in the role of functional and quantitative imaging have led to a surge in research into dose reduction in CT and both structural and functional airway imaging via magnetic resonance imaging. We discuss the current literature on these emerging techniques along with some exiting near future directions for large airways imaging.

Recommendations for patient selection in spinal cord stimulation.

Studies have shown that spinal cord stimulation (SCS) can reduce chronic pain by at least 50% over prolonged periods, improve function and quality-of-life, reduce requirements for healthcare resources and enable return to work in appropriately selected patients. However, SCS does not provide pain relief in all patients and is an expensive, labor intensive and invasive procedure with complications and ongoing management that requires specialists with specific skills and judgment. Multidisciplinary selection of appropriate patients for SCS is essential to achieve maximal benefit from the procedure. The aim of the article is to provide a clinical practice guide to the likely effectiveness of SCS in treating various types of chronic pain, as supported by the literature. The article will summarize indications and contraindications for SCS, provide guidance on the selection and timing for referral, and highlight the benefits and complications associated with the procedure.

Plasminogen activator inhibitor-1 production is pathogenetic in experimental murine diabetic renal disease.

AIMS/HYPOTHESIS: Plasminogen activator inhibitor-1 (PAI-1, also known as serpin peptidase inhibitor, clade E [nexin, plasminogen activator inhibitor type 1], member 1 [SERPINE1]) plays a pathogenetic role in renal fibrosis. It is upregulated in experimental and human diabetic nephropathy. These studies assessed the effect of PAI-1 deficiency and overproduction on renal disease in experimental diabetes. MATERIALS AND METHODS: Diabetes was induced by injection of streptozotocin in 6-week-old PAI-1-deficient mice, transgenic mice overexpressing Pai-1 and control mice. Animals were killed after 24 weeks of diabetes or after observation alone. RESULTS: Pai-1 mRNA was upregulated in kidneys from genetically normal mice with diabetes and in non-diabetic Pai-1 transgenic mice. PAI-1 was not further increased in kidneys from Pai-1 transgenic mice with diabetes. Diabetes-associated albuminuria and glomerular injury, as well as renal alpha-smooth muscle actin production, were ameliorated in diabetic PAI-1-deficient mice, an amelioration associated with attenuated increases in renal matrix metallopeptidase-2 expression and activity. Diabetic Pai-1 transgenic mice did not develop increased albuminuria or glomerular injury, but the tubulointerstitial area was modestly enhanced. In addition to the findings in diabetic mice, abnormalities also developed in 30-week-old PAI-1-deficient and Pai-1 transgenic mice without diabetes. PAI-1 deficiency resulted in increased tubulointerstitial area, TGFB1 protein and alpha-smooth muscle actin. Non-diabetic 30-week-old Pai-1 transgenic mice developed similar renal abnormalities and increased matrix metallopeptidase-2 activity, together with a modest increase in serum glucose and HbA(1c). CONCLUSIONS/INTERPRETATION: These results demonstrate that endogenous PAI-1 deficiency protects mice from glomerular injury in longer term diabetes and that endogenous PAI-1 maintains normal renal interstitial structure in ageing not associated with diabetes.

Anaesthesia in a disaster zone: a report on the experience of an Australian medical team in Banda Aceh following the 'Boxing Day Tsunami'.

We report on the experience of a 23-member Australian medical team in Banda Aceh, Indonesia, following the 2004 Boxing Day tsunami. Arriving 13 days after the tsunami that devastated the city, killed 100,000 of its inhabitants and injured thousands more, we carried out 130 surgical procedures in austere conditions over a 12-day period. Most surgery was peripheral, principally for plastic surgical or orthopaedic procedures to lower limb injuries. Intravenous ketamine anaesthesia was the technique of choice, with good surgical conditions and few significant side-effects.

Pulmonary aspiration of blood following traumatic laryngeal mask airway insertion.

An unusual and potentially life-threatening complication arising from a relatively common event--bleeding due to traumatic laryngeal mask insertion--is presented. It demonstrates that the laryngeal mask airway (LMA) cannot always be relied upon to protect the lower airway from upper airway bleeding.

Pharmacokinetic optimisation of opioid treatment in acute pain therapy.

Traditionally, opioids have been administered as fixed doses at fixed dose intervals. This approach has been largely ineffective. Patient-controlled analgesia (PCA) and upgraded traditional approaches incorporating flexibility in dose size and dose interval, and titration for an effect in individual patients with the monitoring of pain and sedation scores, can greatly improve the efficacy of opioid administration. Optimising opioid use, therefore, entails optimising the titration process. Opioids have similar pharmacodynamic properties but have widely different kinetic properties. The most important of these is the delay between the blood concentrations of an opioid and its analgesic or other effects, which probably relate to the delay required for blood and brain and spinal cord (CNS) equilibrium. The half-lives of these delays range from approximately 34 minutes for morphine to 1 minute for alfentanil. The titration is influenced by the time needed after an initial dose before it is safe to administer a second dose and the duration of the effects of a single dose, which varies widely between opioids, doses and routes of administration. To compare opioids and routes of administration, we examined the relative CNS concentration profiles of opioids - the CNS concentration expressed as a percentage of its maximum value. The relative onset was the defined as the time the relative CNS concentration first rose to 80% of maximum, while the relative duration was defined as the length of time the concentration was above 80%. For an intravenous bolus dose, the relative onset varies from approximately 1 for alfentanil to 6 minutes for morphine, while their relative durations are approximately 2 and 96 minutes, respectively. Although all of the common opioids, perhaps with the exception of alfentanil, have kinetic and dynamic properties suitable for use in PCA with intravenous bolus doses, the long relative duration of morphine makes it particularly suited to an upgraded traditional approach using staff administered intramuscular or subcutaneous doses. There is a clear kinetic preference for regimens with a rapid onset and short duration (e.g. intravenous PCA) for coping with incident pain. It is shown that, in general, titration is improved by the more frequent administration of smaller doses, but it is important to use additional doses to initially 'load' a patient. The titration of opioids should always be accompanied by the monitoring of pain and sedation scores and ventilation.

Morphine blood concentrations in elderly postoperative patients following administration via an indwelling subcutaneous cannula.

The pharmacokinetics of morphine in venous blood after a 5 mg bolus dose via an indwelling subcutaneous cannula were characterised in 22 elderly patients undergoing elective major surgery. In a subgroup of seven patients, the kinetics were also characterised after a second 5 mg dose of morphine administered 180 min after the first dose. Blood morphine concentrations following the single dose were highly variable--the coefficients of variation of Cmax, Tmax and the AUC up to 180 min (AUC180) were 54, 37 and 39%, respectively, with mean values of 86.6 ng.ml-1, 15.9 min and 3954 ng.ml-1, respectively. These mean values for the second dose were not statistically different to those of the first dose but were more variable. It was concluded that the injection of morphine via an indwelling subcutaneous cannula results in blood concentrations that are comparable to, and as variable as, those arising from intramuscular injection.

Multiple cell lines from patients with malignant melanoma: morphology, karyology, and biochemical analysis.

Of 23 cell lines representing 8 patients with malignant melanoma, one cell line from each patient has been extensively characterized by means of phase morphology, ultrastructural morphology, biochemical markers, steroid receptor protein analysis, and steroid hormone production. Extensive cytogenetic characterization was compiled from seven of the eight cell lines. The melanocytic derivation of the tumor cell lines was supported by the detection of the catecholamines epinephrine, norepinephrine, and dopamine. In addition, well-defined melanosomes were present in six of the seven lines whose ultrastructure were examined morphologically. None of the lines produced alpha-fetoprotein chorionic gonadotropin, or carcinoembryonic antigen in detectable amounts. The individuality of the cell lines was confirmed by phenotypic patterns of isozymes and by karyology.

A human gallbladder adenocarcinoma cell line.

A continuous cell line, COLO 346, was established from a liver metastasis in a patient with adenocarcinoma of the gallbladder. COLO 346 grew as an adherent monolayer of pleomorphic epithelioid cells. COLO 346 cells produced esterone, but no estradiol, progesterone, or cortisol. No adrenocorticotropic hormones, beta-subunit of human chorionic gonadotropin, carcinoembryonic antigen, or alpha-fetoprotein production by the cells was detected. Cell doubling time was 36 h. Seven allelic isozymes were assayed. COLO 346 had a chromosome mode of 74 at 21 months postestablishment with 6 marker chromosomes present in 100% of the cells analyzed. COLO 346 has been in continuous culture for over 2 yr and is available to other investigators for their studies.

Characterization of cell lines from four undifferentiated human malignancies.

Tumor tissue from 4 patients with undifferentiated malignancy was studied by means of electron microscopy and cell culture. The cell lines were characterized for morphologic and ultramorphologic appearance, chromosome constitution, and cell products. Cell types established in culture were compared to histologic diagnosis of the original tumor. In only 1 case originally diagnosed as malignant melanoma were cell cultures and ultrastructure consistent with that diagnosis. Two cases in which cell cultures and ultramorphologic appearance were consistent with melanoma were originally diagnosed as carcinoma and sarcoma. The tumor of the fourth patient, diagnosed as melanoma, had no features in the cell cultures and electron micrographs consistent with melanoma. The reliability of using the presence or absence of melanosomes alone as an absolute diagnostic criterion is doubtful.

A human liposarcoma cell line producing hyaluronic acid.

A human liposarcoma cell line COLO 222, derived from a primary tumor in a 62-year-old male, elaborates hyaluronic acid. COLO 222 is characterized on the basis of histochemical, ultramorphological, and cytogenetic properties, along with isozyme phenotype and cell products. A chromosome mode of 53 predominates and unique Giemsa-banded marker chromosomes are identified. An autochthonous lymphoid cell line, COLO 143v, was established after the addition of exogenous Epstein-Barr virus. Cytogenetic analysis of Colo 143v is consistent with a normal male karyotype. COLO 143v possesses B-cell characteristics. This autochthonous system had been used for immunological studies and cytotoxicity assays.

Comparison of four new cell lines from patients with adenocarcinoma of the ovary.

Permanent human tumor cell lines COLO 110, COLO 316, COLO 319, and COLO 330 were established from four patients with serous cystadenocarcinoma of the ovary. COLO 110 was derived from primary tumor tissue; COLO 316, COLO 319, and COLO 330 were derived from cells in malignant effusions. COLO 110 and COLO 316 grew as monolayers of epithelioid cells in culture; COLO 319 and COLO 330 grew as vermiform, floating colonies of epithelioid cells in culture. Epithelial-like morphology was confirmed by transmission electron microscopy. All four cell lines had marker chromosomes and double minute chromosomes. Giemsa banding revealed chromosomes 1, 3, 6, and 7 were involved in markers in all four lines, and chromosomes 2, 4, 5, 9, 11, and 15 were involved in markers in three of the cell lines. Marker chromosomes with possible homogeneous staining regions were observed in COLO 319. Estrone was elaborated by three of the lines, but neither chorionic gonadotropin, carcinoembryonic antigen, nor estrogen or progesterone receptor proteins were detected. Each cell line demonstrated a distinctive isozyme phenotype. These cell lines are maintained in active culture and in a cell bank for distribution to other investigators.

Spontaneous coronary artery perforation with tamponade. Demonstration by necropsy selective coronary arteriography.

Pericardial tamponade in a 51-year-old man after acute anteroseptal myocardial infarction was the result of spontaneous perforation of an atheromatous coronary artery. The value of a simple necropsy technique of selective coronary arteriography in demonstrating the lesion is described.

Tumor and lymphoid cell lines from a patient with carcinoma of the colon for a cytotoxicity model.

Three tumor cell lines (COLO 201, COLO 205, and COLO 206) have been established from ascites fluid obtained from a male patient with adenocarcinoma of the colon. In addition to the tumor lines, two lymphoid lines (COLO 197 and COLO 200) have been established from the same patient, with one line from the original biopsy and one from peripheral blood. Characterization of the tumor cell lines revealed four cell types that differ from most colon cell lines reported by others. Chromosome markers were identical in COLO 201 and COLO 205. A long-arm isochromosome 5 observed in COLO 201 and COLO 205 was absent in COLO 206. Statistical analysis of autosomal polysomy revealed that these cell lines were stable and indicated that there may be a cytogenetic basis for the three predominant types of cell morphology. The lymphoid cell line derived from the peripheral blood had a normal male karyotype. The lymphoid cell line derived from a biopsy specimen had a mode of 46 and a deleted chromosome 7 marker. Both lymphoid cell lines had B-cell characteristics. These autochthonous cell lines have been used for immunological studies in cytotoxicity assays and immunoglobulin characterization.