'Z-Pak' vs ice pack: need for clarity and continuous quality assurance.
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Biomedical subjects
Publications and source records attributed to C Lawyer.
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BACKGROUND: Surgical procedures for emphysema have been proposed and in many settings resulted in significant improvement in dyspnea and function. The most prevalent surgical problem in all series is prolonged postoperative air leak. METHODS: One hundred twenty-three patients undergoing stapled thoracoscopic unilateral lung volume reduction operation were prospectively randomized to receive either no buttressing of their staple lines or buttressing of all staple lines with bovine pericardial strips. RESULTS: The two groups were comparable in preoperative risks and in the severity of their emphysema. Postoperative complications were identical in the two groups with respect to pneumonia, empyema, and wound infection; however, there was a significant difference in the duration of postoperative air leaks. Those having the pericardial strips used to buttress their staple lines had chest tubes removed 2.5 days sooner and were discharged from the hospital 2.8 days sooner as a result. The cost data revealed that because of the cost of the pericardial sleeves, the overall hospital charges were almost identical for the two groups ($22,108 bovine, $22,060 no bovine) in spite of the shortened hospital stay. CONCLUSIONS: The use of bovine pericardial sleeves to buttress the staple lines in thoracoscopic unilateral lung volume reduction operation results in a shorter duration of postoperative air leaks. Total hospital charges were comparable in the two groups as the 2.8 days saved in the hospital were offset by the cost of the pericardial sleeves.
1. The growth inhibitory factor (GIF) is a 68-amino acid protein which is capable of inhibiting the growth of neuronal cells in vitro. 2. We have cloned and sequenced the 5'-flanking region of the mouse GIF gene, which spans from the transcriptional initiation site to the -1854 nucleotide. 3. This region contains sequences homologous to hgcs, SPE, and the JCV silencer domain that functions in a glial cell specific manner. This region also contains two metal responding elements and putative binding sites for AP-1, AP-2, Sp-1, SP-2, NF-1, and CREB. 4. An analysis of the reporter plasmids containing the various regions of the 5'-flanking sequence revealed that the region indeed functioned in a tissue-specific manner in glial cells and that the region between -328 and 175 is responsible for suppression, while the region between -175 and -49 is involved in the activation of gene expression.
It has long been speculated that porcine cathelin is an N-terminal fragment of a longer precursor protein which possesses antimicrobial activity. In an attempt to find such a precursor, a cDNA clone was recently isolated and sequenced by screening a cDNA library from porcine bone marrow. In order to identify the functional activity of the putative protein encoded by an open reading frame, we have synthesized various lengths of peptides that correspond to the C-terminal region of the protein and examined them for their antimicrobial activities. We found that a 13 amino acid tryptophan-rich region with the sequence of VRRFPWWWPFLRR had strong antimicrobial activity with a wide spectrum. It showed potency against Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia, Staphylococcus epidermidis, Proteus mirabilis, and Streptococcus group D as well as Aspergillus fumigatus. The action of this peptide is bactericidal rather than bacteriostatic and this activity is completely inhibited by 2 mM MgCl2. Our results indicate that the previously identified putative precursor encoded by the isolated cDNA indeed possesses a potent antimicrobial activity and that this 13 amino acid synthetic peptide is considered to be a potentially effective drug against various infectious agents.
One hundred forty-one patients were prospectively enrolled in a study of contact-tip laser bullectomy at four institutions. Ninety-one have had both preoperative and postoperative testing at 3 months. Nonsmoking patients with disabling dyspnea at less than 50 yards and with a forced expiratory volume in 1 second of 35% or less were enrolled. Testing included formal pulmonary function tests, arterial blood gasses, computed tomographic scans, ventilation/perfusion scans, echocardiograms, electrocardiograms, 6-minute walk testing, transdiaphragmatic pressures, and quality of life and dyspnea index questionnaires. A modest 16% improvement was noted in forced expiratory volume in 1 second (0.69 to 0.80 L), and there was a 29% improvement in 6-minute walk distances (655.2 to 846.3 feet). Oxygen use was completely discontinued in 16%. Risk factors for mortality included age, 6-minute walk distances, low diffusing capacity for carbon monoxide, high carbon dioxide tension, and high base excess. Minor improvement was judged from the dyspnea index and the Medical Outcome Study Short Form-36. Preoperative predictors of good outcome included heterogeneous disease, lack of carbon dioxide retention, and no emaciation (weight < 40 kg). Comparison of our results with those in the literature suggests that the improvement seen with the contact neodymium:yttrium-aluminum-garnet laser is not as good as that provided by the stapled techniques for volume reduction.
We have synthesized a C-terminal portion of tracheal antimicrobial peptide (TAP) with 38 amino acids and tested it for efficacy on various clinical isolates of Pseudomonas aeruginosa strains from patients with cystic fibrosis and also on Aspergillus fumigatus. Our results indicate that the synthetic TAP has both potent bactericidal and fungicidal activities and that a combination of TAP and amphotericin B showed strong additive effects of growth inhibition on A fumigatus. These results suggest that TAP is potentially an effective therapy for Aspergillus and multi-drug-resistant Pseudomonas, pathogens that are often a serious threat to patients with cystic fibrosis.
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We have chemically synthesized tracheal antimicrobial peptide (TAP) with 38 amino acids and examined efficacy of the peptide on various organisms. The synthetic peptide showed potent bactericidal effect on both gram positive and negative bacteria. The action of bactericidal effect was relatively quick and 99.9% of E. coli cells were killed within 90 minutes at a concentration of 2.5 micrograms/ml of TAP. The peptide also showed antifungal activity against both mycelia (Aspergillus fumigatus) and yeast (Candida albicans) forms of fungi. Our domain analysis with a series of synthetic peptides of various lengths indicates that 17 amino acid residues of the C-terminal end is the minimum functional domain of the bactericidal activity.
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Dihydroxypropyl theophylline (dyphylline) was administered by aerosol in a single dose of 250 mg aerosolized over five minutes to two asthmatic volunteers and in a single dose of 375 mg aerosolized over ten minutes to two other asthmatic volunteers. Serial spirometry was then performed. Marked bronchospasm occurred within ten minutes in two of the subjects, and developed more slowly in another. One subject demonstrated no significant change. Aerosolized dyphylline solution was not an effective bronchodilator, using the methods described in this study.
This study compared the bronchodilator effect in experimental canine asthma of dyphylline administered by aerosol and intravenous routes in doses producing equivalent concentrations of the drug in the plasma. Pulmonary resistance (RL) was calculated from simultaneous measurements of pressure and flow during fixed-volume controlled ventilation at the same peak flow and corrected for elastic recoil pressure. Dynamic compliance (Cdyn) was calculated by dividing tidal volume by the change in pressure measured between points of zero flow. Concentrations of dyphylline in the plasma were measured using high-performance liquid chromatographic techniques. Rates of infusion of dyphylline were determined from values for clearance observed in preliminary experiments with intravenous injection. Prior to exposure to antigen, RL and Cdyn were not significantly different in control and dyphylline-treated dogs. Following challenge, with antigen RL increased by 8.3 +/- 2.6 times (mean +/- SE) in untreated dogs but only by 2.4 +/- 0.4 times in dyphylline treated dogs. Levels of dyphylline in the plasma averaged 4.2 micrograms/ml +/- 0.6 micrograms/ml at the end of the ten-minute period of aerosol administration and remained at that level for 60 minutes. At equivalent plasma levels (4.3 micrograms/ml +/- 0.3 micrograms/ml), infusion of dyphylline did not significantly after the response to Ascaris antigen, whereas dyphylline administered by the aerosol route markedly attenuated the response.
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The recently discovered human herpesvirus-6 (HHV-6) is being associated with an increasing number of conditions in which there is evidence of immunologic dysfunction. A number of widely available antiviral agents have shown little or no activity against the virus. We found that Kutapressin (KU), a drug that has been available to practicing physicians for over 50 years, has potent, previously unexpected antiviral effects. Cells known to allow replication of HHV-6 were infected with the virus, under various conditions. Either pretreatment of the cells prior to infection or treatment shortly after infection, inhibited viral replication by > 90%. Indirect evidence suggests that KU may inhibit viral attachment to cellular receptors, and inhibit intracellular maturation of the virus. Given these in vitro findings, and the low frequency of toxicity reported with the use of KU, clinical trials of this drug in patients with evidence of reactivated HHV-6 infection would seem to be warranted.
BACKGROUND: Kutapressin (KU), a porcine liver extract with bradykinin-potentiating effects but no vitamin B 12 activity, has been used in the treatment of Herpes zoster. We examined a phenol-free preparation of this drug for in vitro activity against Epstein-Barr Virus (EBV). MATERIALS AND METHODS: Immortalization-inhibition assays were used to assess EBV infectivity. Mitogen stimulation and cell viability assays were used to assess kutapression toxicity. Lytic replication assays and flow cytometry were used to assess the mechanism of drug activity. RESULTS: Seventy-five hundred mcg/ml of KU blocked the infection of 2 x 10(5) human umbilical cord mononuclear cells when added together with two strains of EBV (B95-8 and FF41). Doses as low as 250 mcg/ml were occasionally effective as well. Unlike acyclovir, KU does not inhibit viral DNA polymerase nor does it appear to compete with EBV as it binds to its receptor on the B-cell surface. CONCLUSIONS: The mechanism whereby KU may inhibit EBV immortalization remains to be determined. KU, a drug which is safe in humans, deserves further study as an agent with potential to block EBV-induced immortalization of B-lymphocytes.