β-Adrenergic Desensitization after Burn Excision Not Affected by the Use of Epinephrine to Limit Blood Loss

Background: Burn patients have impaired myocardial function and decreased [beta]-adrenergic responsiveness. Further [beta]-adrenergic dysfunction from systemic absorption of topically administered epinephrine that is given to limit blood loss during burn excision could affect perioperative management. The authors evaluated the effect of topical epinephrine administration to patients during burn excision on the lymphocytic [beta]-adrenergic response.

Methods: Fifty-five patients (age, 2-18 yr) with 20-90% body surface area burns received a standardized anesthetic for a burn excision procedure. Lymphocyte samples were taken at baseline and 1 and 3 h after the initial use of epinephrine (n = 43) or thrombin (controls, n = 12). Plasma epinephrine levels were measured by high-performance liquid chromatography. Lymphocyte [beta]-adrenergic responsiveness was assessed by measuring production of cyclic adenosine monophosphate (cAMP) after stimulation with isoproterenol, prostaglandin E1 (PGE1), and forskolin. [beta]-adrenergic receptor binding assays using iodopindolol and CGP12177 yielded [beta]-adrenergic receptor density.

Results: Epinephrine levels were elevated at 1 h (P < 0.01) and 3 h (P < 0.01) after epinephrine use but not in control patients. Production of cAMP in lymphocytes 1 h after epinephrine was greater in patients receiving epinephrine than in control patients on stimulation with isoproterenol (P < 0.05) and PGE1 (P < 0.05). Three hours after epinephrine administration, production of cAMP decreased when compared with baseline in both control patients and those receiving epinephrine after stimulation with isoproterenol (P < 0.05), PGE1(P < 0.05), and forskolin (P < 0.05). Lymphocytic [beta]-adrenergic receptor content was not changed.     

Angiographic distribution of lower extremity atherosclerosis in patients with and without diabetes.

AIMS: To determine differences in the anatomic site of atherosclerosis in the lower extremity between patients with and patients without diabetes. DESIGN: Cross-sectional study of patients who underwent angiography of both legs because of symptoms of intermittent claudication, rest and/or night pain, ulceration or gangrene. METHODS: The angiographies of 37 patients with diabetes and 37 patients without diabetes, matched for age, sex and smoking behaviour, were evaluated using the Bollinger scoring system. RESULTS: The mean (sd) Bollinger score in the upper leg (from the abdominal aorta to and including the superficial femoral artery) was higher (P = 0.01) for patients without diabetes (35.3 (22.8)) than for patients with diabetes (23.3 (16.1)). In the lower leg (from the popliteal artery to the posterior tibial artery) patients with diabetes tended to have a higher score than patients without diabetes: 47.4 (34.2) and 37.6 (32.9), respectively (P = 0.22). CONCLUSION: This angiographic study confirms the clinical notion that lower limb atherosclerosis in diabetes is more severe in distal segments of the lower extremity, while the proximal segments remain less attenuated compared with patients without diabetes.     

Results of percutaneous transluminal angioplasty in renal artery stenosis during the period 1978-1986

Two hundred and thirteen patients with hypertension and renal artery stenosis were treated with percutaneous transluminal renal angioplasty (PTRA). The angiographic appearance was typical of atherosclerosis in 134 patients and of fibromuscular dysplasia (FMD) in 52 patients, and could not reliably be classified in one of these groups in 27. In these patients 272 renal artery stenoses were treated. In 81% of these patients the PTRA was technically successful. The antihypertensive result in this group of 210 patients was positive (cure or improvement) in 80%. The life-table results after 5 years show cure or improvement in the atherosclerotic group (n = 35) in 80.27%, in the FMD group (n = 20) in 88.83% and in the unclassified group (n = 10) in 74.27%. One patient died from a mesenteric thrombosis and one from a myocardial infarction which both occurred within a few days after PTRA. Accordingly, the mortality was less than 1%. In conclusion: PTRA appears to be a good treatment of renovascular hypertension caused by atherosclerosis or FMD, with good long-term antihypertensive effects.     

The relation between Helicobacter pylori and atherosclerosis cannot be explained by a high homocysteine concentration

BACKGROUND: Recent studies have suggested that a chronic infection with Helicobacter pylori might be an independent risk factor for atherosclerosis. However, a direct role in atherogenesis is not plausible, since the bacterium has not been isolated from atherosclerotic lesions. An indirect mechanism that could link H. pylori with atherosclerosis might be through an increase in plasma homocysteine concentration caused by deficiencies of vitamin B12 and folate in plasma. MATERIALS AND METHODS: In 150 female patients with peripheral arterial disease (PAD) and in 412 healthy control women from a nation-wide population-based case-control study, blood samples were collected to determine the antibody titre against H. pylori and to measure plasma homocysteine, folate and vitamin B12 levels. First, the odds ratio for PAD in women with a positive antibody titre against H. pylori was calculated and adjusted for homocysteine level. Secondly, mean concentrations of vitamin B12, folate and homocysteine were compared in healthy controls with a positive or negative antibody titre against H. pylori. Thirdly, the relation between H. pylori and PAD in individuals with a normal or high homocysteine level was investigated. RESULTS: A positive immunoglobulin G antibody titre against H. pylori was found in 42% of the PAD patients and in 27% of the controls. The age- and socio-economic-status (SES) adjusted odds ratio for PAD was 1.5 (95%CI; 1.0-2.2). Additional adjustment for homocysteine plasma concentration did not essentially change the odds ratio. Secondly, among the healthy controls, the homocysteine plasma concentration did not depend on the immunoglobulin G titre, neither did the folate plasma concentration. The concentration of vitamin B12 was slightly higher in women with a positive titre. Thirdly, H. pylori infection was a risk factor for PAD in subjects with a normal homocysteine concentration [OR 2.0 (95%CI 1.3-3.1)]. CONCLUSIONS: This study shows a relationship between a positive immunoglobulin G antibody titre against H. pylori and PAD in young women. Moreover, this study does not support the hypothesis that H. pylori infection is related to atherosclerosis via an increase in plasma homocysteine concentration.     

Inhaled nitric oxide reverses cell-free hemoglobin-induced pulmonary hypertension and decreased lung compliance. Preliminary results

Background

In order to test the hypothesis that inhaled nitric oxide (NO) reverses the pulmonary hypertension induced by αα-diaspirin crosslinked hemoglobin (ααHb), were studied anesthetized pigs that were administered with a total dose of 200 mg/kg of 10% ααHb. Inhaled NO (5 ppm) was administered for 10 min, and then discontinued for 10 min. This cycle was then repeated with 10 ppm inhaled NO.

Results

ααHb caused pulmonary arterial pressure (PAP) to increase from 27 ± 1.7 to 40 ± 3.0 mmHg (P<0.05) and dynamic lung compliance to decrease from 29± 1.5 to 23± 1.6 ml/cmH₂O (P < 0.05). After both doses of inhaled NO, but particularly 10 ppm, PAP was reduced (P < 0.05) and lung compliance increased (P < 0.05) from the ααHb levels. When inhaled NO was discontinued PAP again increased and lung compliance decreased to levels significantly different from baseline (P < 0.05).

Conclusion

We conclude that cell-free hemoglobin-induced pulmonary hypertension and decreased lung compliance can be selectively counteracted by inhaled NO.     

Mild to Moderate Intrapulmonary Shunting in Pediatric Liver Transplantation: Is Screening Necessary?

Background

Despite reported associations between intrapulmonary vascular shunting (IPVS) and morbidity and mortality in pediatric liver transplantation (LT), there are no guidelines for screening.

S6K1 regulates hematopoietic stem cell self-renewal and leukemia maintenance

Hyperactivation of the mTOR pathway impairs hematopoietic stem cell (HSC) functions and promotes leukemogenesis. mTORC1 and mTORC2 differentially control normal and leukemic stem cell functions. mTORC1 regulates p70 ribosomal protein S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E–binding (eIF4E-binding) protein 1 (4E-BP1), and mTORC2 modulates AKT activation. Given the extensive crosstalk that occurs between mTORC1 and mTORC2 signaling pathways, we assessed the role of the mTORC1 substrate S6K1 in the regulation of both normal HSC functions and in leukemogenesis driven by the mixed lineage leukemia (MLL) fusion oncogene MLL-AF9. We demonstrated that S6K1 deficiency impairs self-renewal of murine HSCs by reducing p21 expression. Loss of S6K1 also improved survival in mice transplanted with MLL-AF9–positive leukemic stem cells by modulating AKT and 4E-BP1 phosphorylation. Taken together, these results suggest that S6K1 acts through multiple targets of the mTOR pathway to promote self-renewal and leukemia progression. Given the recent interest in S6K1 as a potential therapeutic target in cancer, our results further support targeting this molecule as a potential strategy for treatment of myeloid malignancies.