Estrogen-induced refractoriness to the pressor effects of infused angiotensin II

Estrogen may be important in the hemodynamic changes that develop during pregnancy; its role in the development of vascular refractoriness to the pressor effects of infused angiotensin II is unknown. We, therefore, examined the pressor responses to six doses of angiotensin II (0.115 to 5.73 micrograms/min) in unanesthetized, nonpregnant sheep both before and after treatment with either high-dose or low-dose 17 beta-estradiol (E2) and constructed dose-response curves. Although mean arterial pressure was unchanged after the infusion of E2, cardiac output rose 28% and systemic vascular resistance fell 19% (p less than 0.001). Infused angiotensin II resulted in dose-dependent rises in mean arterial pressure before and after E2; however, the pressor response after E2 was decreased 30% to 50%. Plasma renin activity rose from 1.15 +/- 0.09 ng/ml X hr to 2.57 +/- 0.39 and 3.21 +/- 0.61 ng/ml X hr with low-dose and high-dose E2, respectively (p less than 0.05). Acutely estrogenized nonpregnant sheep develop significant alterations in both the cardiovascular and the renin-angiotensin systems in addition to decreased pressor responsiveness to infused angiotensin II. Although our findings suggest that estrogen may be important in the development of the vascular refractoriness to angiotensin II seen in pregnancy, additional studies are needed to clarify the role of each E2-induced change.     

Evidence of alpha 2-adrenoceptors in the nasal blood vessels of the dog

alpha-Adrenoceptor subtypes were demonstrated in an in vitro preparation of the vascular smooth muscle of the canine nasal mucosa. alpha 1-Receptors were located on the surface of vascular smooth muscle (postsynaptic). alpha 2 Subtypes were situated both at postsynaptic and presynaptic sites on adrenergic nerve terminals. Presynaptic alpha 2-adrenoceptor stimulation yielded an inhibition of excessive norepinephrine release from nerve terminals. Stimulation of postsynaptic receptors, either alpha 1 or alpha 2, produced vasoconstriction. Although there was good evidence of the presence of postsynaptic alpha 2-receptors, they did not appear to be dominant among the postsynaptic receptors.     

Royal Australian College of Ophthalmologists and Royal Australian College of General Practitioners National GP Eye Skills Workshops: colleges and divisions reskilling general practice

Purpose : Little formal eye skills training has historically been available to Australian general practitioners at undergraduate or postgraduate levels. The development of the National GP Eye Skills Workshop was a joint initiative of the Royal Australian Colleges of General Practice and Ophthalmology, to enhance the skills of Australian general practitioners in a range of important ocular examination and procedural areas. Methods : Workshops were run in eight Queensland Divisions of General Practice in 1998. Between two and 10 local ophthalmologists in each divisional area were involved either in the workshop programme or in the recruitment of patients for the patient assessment module. Workshops were run on weekends and included modules on vision testing and disease screening in children and adults, ophthalmoscopy, assessment for glaucoma and diabetic retinopathy, incision of chalazions, removal of corneal foreign bodies, ocular first aid, implementing eye assessment in busy general practice, and a patient assessment clinic. A questionnaire was administered which was comprised of sections relating to the format of the workshop, new skills and concepts learnt, learning exceptions, and perception of future ability to treat/scan/assess for eye conditions in general practice. The questionnaire was completed by 91% of participants. Results : Participants strongly supported the impact of the workshop on their ability to detect and treat eye problems in their practices, and refer where appropriate to an ophthalmologist. They also rated highly all individual aspects of the programme in terms of impact on their delivery of general practitioner eye care. Conclusions : The results illustrate the comprehensive success of the workshop programme in format, content, relevance and delivery.     

Sclerosing peritonitis complicating continuous ambulatory peritoneal dialysis managed by hemodialysis and home parenteral nutrition

A 47-year-old dialysis patient developed severe sclerosing peritonitis. The patient has been unable to take any nutrition by mouth for 27 months. She has been maintained daily on home parenteral nutrition and hemodialysis 3 times per week. It has been possible for her to have a good quality of life and to maintain good nutritional status.     

The effect of anticoagulation therapy and graft selection on the ischemic consequences of femoropopliteal bypass graft occlusion: results from a multicenter randomized clinical trial

OBJECTIVE: A recent retrospective study showed that the ischemic consequences of femoropopliteal bypass graft occlusion were more severe with polytetrafluoroethylene (PTFE) than with vein. This study examines this conclusion and whether oral anticoagulation therapy reduces the degree of ischemia after occlusion of PTFE and vein femoropopliteal bypass grafts. METHODS: Four hundred two patients who underwent femoropopliteal bypass grafting (233 PTFE and 169 vein) were randomized to a postoperative regimen of either warfarin (international normalized ratio, 1.4 to 2.8) and aspirin (WASA; 325 mg daily) therapy or aspirin alone (ASA) therapy. The grade of acute ischemia at the time of graft occlusion was assessed with the Society of Vascular Surgery recommended reporting standards (I, viable; II, threatened). Early graft occlusions (<30 days) were excluded. RESULTS: There were 100 graft occlusions (67 PTFE and 33 vein) during a mean follow-up period of 36 months (PTFE) and 39 months (vein). Forty-eight patients were randomized to WASA therapy, and 52 were randomized to ASA therapy. The patients were well matched for age, atherosclerotic risk factors, operative indication, and preoperative ankle-brachial index. Overall, a greater percentage of the PTFE occlusions caused grade II ischemia than did the vein graft occlusions (48% versus 18%; P =.005). The ankle-brachial index at the time of graft occlusion was significantly lower in the PTFE grafts than in the vein grafts (0.28 versus 0.45; P =.001). The patients with PTFE who were undergoing WASA therapy at the time of graft occlusion had less grade II ischemia than did those patients who were undergoing ASA therapy (28% versus 55%; P =.057). However, the incidence rate of severe ischemia after graft occlusion remained greater with PTFE grafts and WASA therapy as compared with all the vein grafts (28% versus 18%). The vein graft occlusions had the same incidence rate of grade II ischemia with WASA therapy as with ASA therapy (20% versus 17%; P = 1.0). CONCLUSION: The ischemic consequences of femoropopliteal bypass graft occlusion are worse with PTFE than with vein. Treatment with WASA therapy lessens the severity of acute ischemia after the occlusion of PTFE graft as compared with ASA therapy but not to the degree seen with vein graft occlusion. Occlusion of femoropopliteal vein grafts is seldom accompanied by severe ischemia and is not improved with WASA therapy.     

The prevalence of soft tissue injuries in nonoperative tibial plateau fractures as determined by magnetic resonance imaging

OBJECTIVE: To determine the incidence of meniscus tears and complete ligament disruption in nondisplaced and minimally displaced tibial plateau fractures, which are otherwise amenable to nonoperative management. DESIGN: Prospective clinical study. SETTING: Level I urban trauma center. INTERVENTION: Magnetic resonance imaging of 20 consecutive nonoperative tibial plateau fractures. RESULTS: Magnetic resonance imaging was performed on 20 consecutive nonoperative (nondisplaced or minimally displaced) tibial plateau fractures to determine the frequency of significant soft tissue injuries. Ninety percent (18 of 20) had magnetic resonance imaging-diagnosed significant injuries to the soft tissues, including 80% (16 of 20) with meniscal tears, and 40% (8 of 20) with complete ligament disruptions. CONCLUSIONS: This study found a high prevalence of soft tissue injuries with nondisplaced fractures of the tibial plateau and cautions the physician and patient with respect to future knee function and possible arthrosis.     

Angiotensin-converting enzyme genotype and outcome in pediatric IgA nephropathy

Angiotensin-converting enzyme (ACE) I/D polymorphism has been implicated as a genetic marker for progression of glomerular disease. Studies of ACE genotypes in adults with IgA nephropathy (IgAN) have yielded conflicting results. We performed ACE genotyping on 79 patients with IgAN diagnosed prior to age 18 years who had either progressed to end-stage renal disease (ESRD) or are now more than 5 years post biopsy. Mean follow-up was 14.8 years for those with normal renal function. Forty-three (54.4%) subjects had normal renal function and a normal urinalysis at last evaluation. Sixteen (20%) progressed to ESRD and 1 has chronic renal insufficiency. Kaplan-Meier survival curves for progression to ESRD did not differ significantly for the ACE DD, ID, and II genotype groups (P=0.095, log-rank test). By univariate analysis, presence of hypertension and degree of proteinuria at diagnosis, and unfavorable histology but not ACE genotype, was significantly associated with progression to ESRD. In the Cox proportional hazards model that included grade of proteinuria, the ACE D allele was a significant independent predictor of outcome with a hazard ratio of 2.37 (P=0.031). Our data, while inconclusive, suggest that the ACE D allele may associate with poor outcome in pediatric IgAN.     

Induction of chimerism in mice using human MHC class I-mismatched Hoechst 33342 side population donor stem cells

A population of Hoechst 33342-stained cells, termed side population (SP) cells, can reconstitute the hematopoietic system of syngeneic mice. This study examined whether limiting numbers of SP cells can repopulate mice across a xenogeneic MHC class I barrier. SP cells were isolated from HLA.B7 and HLA.A2.1 transgenic mice by FACS and placed in colony assays or transplanted into irradiated C57BL/6 (B/6) recipients. SP cells contained few colony-forming cells when placed directly in culture. The number of GM-CFC and HPP-CFC increased up to 3000- and 300-fold, respectively, after 7 days in IL-3- and SCF-stimulated liquid culture. BMC-derived GM-CFC increased up to only 12-fold and HPP-CFC decreased after 7 days in culture. HLA-B7 SP cells (2500-5000) were transplanted into lethal-irradiated B/6 mice. Two-color flow analysis, 4-6 weeks after transplantation, showed that HLA-B7 expression in granulocyte-, macrophage-, and lymphocyte-specific lineages from reconstituted mice was similar to that in B7 transgenic mice. Secondary transplanted B/6 mice also showed a pattern of HLA-B7 expression similar to that in transgenic mice and were followed for longer than 16 weeks with stable chimerism. When HLA-A2.1 SP cells were transplanted into sublethally irradiated mice, 50% of the mice expressed HLA-A2 by PCR analysis in short-term repopulation studies. These data confirm that limiting numbers of SP cells can repopulate the major hematopoietic lineages in lethal and sublethally irradiated mice across a human MHC class I barrier. Therefore, SP cells may be useful for establishing mixed chimerism, which may induce immunologic nonresponsiveness to donor antigens in solid organ transplantation.     

Lymphatic vessels in vascularized human corneas: immunohistochemical investigation using LYVE-1 and podoplanin

PURPOSE: To determine whether lymphatic vessels exist in vascularized human corneas, by using immunohistochemistry with novel markers for lymphatic endothelium. METHODS: Human corneas exhibiting neovascularization secondary to keratitis, transplant rejection, trauma, and limbal insufficiency (n = 21) were assessed for lymphatic vessel content by conventional transmission electron microscopy and by immunostaining and immunoelectron microscopy with antibodies specific for the lymphatic endothelial markers, lymphatic vessel endothelial hyaluronan receptor (LYVE-1) and the 38-kDa integral membrane glycoprotein podoplanin. In addition, corneas were stained for the lymphangiogenic growth factor VEGF-C, and its receptor VEGFR3 by immunohistochemistry and in situ RNA hybridization, respectively. RESULTS: Thin-walled, erythrocyte-free vessels staining with lymphatic markers (LYVE-1 and podoplanin) were found to constitute 8% of all vessels, to be more common in the early course of neovascularization, to be always associated with blood vessels and stromal inflammatory cells, and to correlate significantly with the degree of corneal hemangiogenesis (r = 0.6; P = 0.005). VEGF-C, VEGFR3, podoplanin, and LYVE-1 colocalized on the endothelial lining of lymphatic vessels. With immunogold labeling, LYVE-1 and podoplanin antigen were found on endothelial cells lining vessels with ultrastructural features of lymph vessels. CONCLUSIONS: Immunohistochemistry with novel lymph-endothelium markers and ultrastructural analyses indicate the existence of lymphatic vessels in vascularized human corneas. Human corneal lymphangiogenesis appears to be correlated with the degree of corneal hemangiogenesis and may at least partially be mediated by VEGF-C and its receptor VEGFR3.