The pharmacokinetics of 125I-atrial natriuretic factor in anaesthetized rats. Effects of neutral endopeptidase inhibition with candoxatrilat and of ANF-C receptor blockade.

The effects of candoxatrilat (cis-4-([2-carboxy-3-(2-methoxyethoxy)propyl]-1-cyclopentanecarbonyla mino)- 1-cyclohexane carboxylic acid) and the ring-deleted atrial natriuretic factor (ANF) analogue C-ANF4-23 (des[Gln18, Ser19, Gly20, Leu21, Gly22]ANF4-23-NH2) on the clearance of (3-[125I]iodotyrosyl28)ANF (125I-ANF) were studied in both intact and nephrectomized anaesthetized rats. HPLC analysis was used to verify that the 125I-labelled material isolated by solid phase extraction of rat plasma was intact ANF. In intact animals, clearance of 125I-ANF was biphasic with a T1/2 alpha of 17 sec and T1/2 beta of 95 sec. Volume of distribution (Vd) was 564 mL/kg and plasma clearance (Clp) 248 mL/min/kg. Candoxatrilat, over the dose range 0.01-10 mg/kg i.v., increased T1/2 beta (by a maximum of 56%) and decreased Clp (by up to 52%) with no effect on T1/2 alpha or Vd. C-ANF4-23 (10 micrograms/kg+1 microgram/kg/min i.v.) reduced Vd (by 57%) and Clp (by 54%) with no effect on T1/2 beta, whilst abolishing the T1/2 alpha phase in over 50% of animals. Increasing the dose of C-ANF4-23 did not increase the effect on any of these parameters, apart from a small increase in T1/2 beta. Combining the two agents resulted in a substantial decrease in Clp (76%) whilst the reduction in Vd and increase in T1/2 beta were comparable to those seen with C-ANF4-23 and candoxatrilat alone, respectively. In nephrectomized rats, the pharmacokinetics of 125I-ANF and the changes induced by candoxatrilat were similar to those observed in intact animals, whilst the effects of C-ANF4-23 alone were greater than in intact animals. The combination of C-ANF4-23 and candoxatrilat again produced a substantial increase in T1/2 beta (153%) and decreases in Vd (55%) and Clp (78%) in nephrectomized animals, although these changes could not be distinguished from those seen in intact animals treated with the same combination. Our studies indicate that neutral endopeptidase and ANF-C receptors are both major, and approximately equal, clearance mechanisms for 125I-ANF, together accounting for at least 75% of the total clearance of this peptide in the rat.     

Extending community health nursing services. The Student Learning Center.

Faced with scarce resources, the Visiting Nurse Association of Omaha (VNA), Bishop Clarkson College, Creighton University, and University of Nebraska Medical Center collaborated to maintain services. Baccalaureate students learned to deliver community health nursing while serving a population in need of these services, but not coverable by funding sources. The Student Learning Center established by the VNA enabled 254 students to provide 5,035 home visits to families without funding sources.     

An experimental painful peripheral neuropathy due to nerve constriction. I. Axonal pathology in the sciatic nerve.

A constriction injury to the sciatic nerve of the rat produces a painful peripheral neuropathy that is similar to the conditions seen in man. The pathology of the sciatic nerve in these animals was examined at 10 days postinjury, when the abnormal pain sensations are near maximal severity. The nerves were examined with (1) complete series of silver-stained longitudinal sections of pieces of the nerve (3 cm or more) that contained the constriction injury in the center, (2) toluidine blue-stained semithin sections taken at least 1 cm proximal and 1 cm distal to the constriction, and (3) EM sections taken adjacent to those stained with toluidine blue. One centimeter or more proximal to the constriction, both myelinated and unmyelinated axons were all normal. Nearer to the constriction, extensive degeneration of myelinated axons became increasingly common, as did signs of endoneurial edema. Distal to the constriction, the nerve was uniformly edematous and full of myelinic degeneration. There was a profound loss of large myelinated axons and a distinctly less severe loss of small myelinated and unmyelinated axons. These observations show that at 10 days postinjury the constriction produces a partial and differential deafferentation of the sciatic nerve's territory. The absence of degeneration in the nerve 1 cm proximal to the constriction indicates the survival of the primary afferent neurons whose axons are interrupted.     

Spontaneous migration of an inferior vena cava filter resulting in cardiac tamponade and percutaneous filter retrieval.

Thromboembolic disease accounts for thousands of hospitalizations every year in the US. Its primary management consists of anticoagulation. However, in certain instances this may be contraindicated or not sufficient. Mechanic occlusion of the inferior vena cava (IVC) becomes then a viable alternative. In this case a 35-year-old man presented with a saddle pulmonary embolus but was unable to be anticoagulated due to intestinal bleed. A removable IVC filter was then placed. The filter spontaneously migrated into the right atrium causing severe tricuspid regurgitation, perforation of the atrial wall, and cardiac tamponade. The device was successfully retrieved percutaneously and the patient discharged from the hospital in stable condition. This case illustrates the potentially lethal complications associated with the use of IVC filters, as well as the possibility to percutaneously recover them from within the right atrium.     

An internet survey of 2,596 people with fibromyalgia

Background  

This study explored the feasibility of using an Internet survey of people with fibromyalgia (FM), with a view to providing information on demographics, sources of information, symptoms, functionality, perceived aggravating factors, perceived triggering events, health care utilization, management strategies, and medication use.     

Significance of the early postoperative duplex result in infrainguinal vein bypass surveillance.

BACKGROUND: Duplex surveillance of infrainguinal vein grafts may not be efficient. METHODS: Consecutive patients who had received infrainguinal vein grafts were enrolled in a duplex surveillance program. A first scan at 6 weeks after surgery categorized grafts into four groups: (a) low risk grafts, (b) mild flow disturbance, (c) intermediate stenosis and (d) critical stenosis. Disease progression was assessed over time. RESULTS: Of 364 grafts followed-up for a median of 23 months, 236 (65%) had no flow abnormality at 6-weeks, and had a 40-month cumulative patency rate of 82%. The remaining 128 (35%) grafts had a flow disturbance. Of 29 critical stenoses, 15 were repaired, 11 occluded and three did not change. Of 57 intermediate lesions, 32 progressed to critical, nine occluded, two were repaired and 14 did not change or improved. Of 42 mild lesions, 16 progressed to a higher grade, four occluded and 22 did not change or improved. There was no significant difference in graft patency between grafts with repaired stenoses and those without stenoses, but grafts with untreated critical stenoses were associated with lower patency (p<0.001). CONCLUSIONS: A duplex scan 6 weeks after operation can predict those patients who require continuing duplex surveillance.