Protein kinase-A and the effects of parathyroid hormone on phosphate uptake in opossum kidney cells

Current evidence indicates that signal transduction after receptor binding of PTH involves the stimulation of adenylate cyclase as well as stimulation of phosphoinositide metabolism. Recent studies, showing that PTH alters phosphate transport in opossum kidney cells at concentrations which do not increase cAMP production and that activators of protein kinase-C also alter phosphate transport, have led to the suggestion that there is a dual mechanism for the regulation of phosphate transport by PTH, namely, protein kinase-C at physiological levels of PTH and cAMP at higher levels of PTH. The present studies were designed to evaluate the relationship between cAMP-dependent protein kinase (PK-A), a more sensitive indicator of alterations in cAMP metabolism than measurements of total cellular cAMP, and phosphate transport in opossum kidney cells, in response to bovine (b)PTH 1-34 and [Nle8,Nle18,Tyr34]bPTH 3-34 amide. While bPTH 1-34 markedly stimulated cAMP accumulation (half-maximal stimulation between 1 and 10 nM), PTH 3-34 analog did not. Phosphate transport was inhibited in a dose-dependent manner by bPTH 1-34, with half-maximal effect occurring between 0.1 and 1 nM. [Nle8,Nle18,Tyr34]bPTH 3-34 amide also altered phosphate transport, although this peptide was 3 orders of magnitude less potent than bPTH 1-34. PK-A activity increased in response to bPTH 1-34 and correlated closely with the effects of PTH on phosphate transport. [Nle8,Nle18,Tyr34]bPTH 3-34 amide, which did not appear to increase cAMP, also resulted in a significant increase in the activity of PK-A. Studies of inhibition of cAMP accumulation using 2',5'-dideoxyadenosine demonstrated that while this agent markedly inhibited the accumulation of cAMP in response to PTH, the effects of PTH on phosphate transport were not altered. However, in spite of the reduction in cAMP the activation of PK-A was similar to control. These data indicate that the effects of PTH peptides on phosphate transport are more closely related to changes in the activity of PK-A than to levels of total cAMP. Activation of PK-A in response to PTH is demonstrable at the lowest doses of PTH that alter phosphate transport.     

FM sonography in diffuse liver disease: prospective assessment and blinded analysis

FM sonography - a signal-processing technique that uses frequency and phase information as well as amplitude data - shows promise in evaluation of patients with diffuse liver disease. In a prospective blinded review of 37 patients with biopsy-proved liver disease and 42 healthy volunteers, FM sonography was clearly superior to traditional amplitude-based (AM) sonography in distinguishing healthy from diseased subjects. Statistically significant differences were seen in accuracy (FM, 98.7%; AM, 84.8%), sensitivity (FM, 97.3%; AM, 70.3%), and negative predictive value (FM, 97.7%; AM, 78.8%). Our data also suggest that current FM sonographic techniques cannot differentiate among histologic findings associated with different hepatic parenchymal abnormalities. It is unclear, therefore, whether FM imaging can reduce the numbers of patients who require biopsy for diagnosis or the frequency of biopsy procedures in patients with known disease.     

Development of a new wound dressing with antimicrobial delivery capability

A bilaminar wound dressing composed of an outer membrane and an inner three-dimensional matrix of a fabric or a sponge may be considered to constitute an ideal structure that promotes wound healing: the outer membrane prevents body fluid loss, controls water evaporation, and protects the wound surface from bacterial invasion, and the inner matrix encourages adherence by tissue growth into the matrix. Using this concept, we developed a biosynthetic wound dressing with a drug delivery capability. This medicated wound dressing is composed of a spongy sheet of a chitosane derivative and collagen mixture that is laminated to an antimicrobial-impregnated polyurethane membrane. In this study, a gentamycin sulfate-impregnated wound dressing was prepared and evaluated. The antimicrobial efficacy of this wound dressing was examined on an agar plate seeded with Pseudomonas aeruginosa. Also, the cytotoxicity of an antimicrobial released from this wound dressing was examined in an in vitro system with cultured skin substitutes. Both in vitro tests have shown that this wound dressing is capable of suppressing bacterial growth and minimizing cellular damage. In addition, in the treatment of wounds inflicted on rats and rabbits, this wound dressing was shown to be efficacious in covering full-thickness and split-thickness skin defects. Finally, the efficacy of this wound dressing was evaluated in a nonrandomized open-label study of 31 clinical cases. In 31 cases treated with this wound dressing, good or excellent wound healing was achieved.     

Use of a Strecker oesophageal stent in the treatment of benign oesophageal stricture

The use of self-expanding prostheses in the management of malignant oesophageal strictures has become well established. The majority of benign peptic oesophageal strictures can be successfully managed using endoscopic or fluoroscopically guided balloon oesophageal dilatation combined with long-term drug therapy, particularly using proton pumper inhibitors. Although endoscopic oesophageal dilatation can be performed on an outpatient basis, it requires repeated hospital visits. There is a small risk of oesophageal perforation whilst cardio-respiratory complications may be encountered during the use of intravenous sedation in an elderly population. The use of a self-expanding Strecker stent in a 98 year old woman with a benign oesophageal stricture is described.     

Asbestos-related focal lung masses: manifestations on conventional and high-resolution CT scans

In 260 asbestos-exposed individuals evaluated by means of computed tomography (CT), 43 unsuspected pulmonary masses were found in 27 individuals. The masses included fissural pleural plaques (n = 10), dense fibrotic bands (n = 3), round atelectasis (n = 11), carcinomas (n = 3), and other presumed benign masses (n = 16). The most helpful features in the diagnosis of rounded atelectasis with CT were (a) contiguity to areas of diffuse pleural thickening, (b) a lentiform or wedge-shaped outline, (c) evidence of volume loss in the adjacent lung, and (d) a characteristic "comet tail" of vessels and bronchi sweeping into the margins of the mass. Less advanced areas of focal atelectasis had fewer classic features. Intrafissural pleural plaques were readily identified with high-resolution CT. In asbestos-related masses, the demonstration of stability over time is necessary. Careful interpretation of CT and high-resolution CT features and close surveillance can obviate the need for biopsy in the majority of instances.