Nuclear magnetic resonance studies of lithium transport in erythrocyte suspensions of hypertensives

We have applied a nuclear magnetic resonance (NMR) method, based on the 7Li nucleus, to discriminate between intracellular and extracellular lithium ions (Li+) in red blood cell (RBC) suspensions. The NMR method was compared with atomic absorption, a technique that requires physical separation of intra- and extracellular Li+ prior to chemical analysis. The rates and rate constants of RBC Na(+)-Li+ countertransport measured by the 7Li NMR method correlated significantly with the measurements made by atomic absorption for both the hypertensive (r = 0.964) and control (r = 0.961) groups. The rates of RBC Na(+)-Li+ countertransport measured by NMR were significantly higher for hypertensive patients than for normotensive controls. The fact that the NMR method does not require cell membrane lysis, and its potential to reveal structural and mechanistic information on Li+ binding and transport in cellular systems, makes it promising for understanding the basis of Li+ transport variations in RBCs, and possibly other tissues, from hypertensive patients.     

Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability.

Vulnerable areas of atherosclerotic plaques often contain lipid-laden macrophages and display matrix metalloproteinase activity. We hypothesized that reactive oxygen species released by macrophage-derived foam cells could trigger activation of latent proforms of metalloproteinases in the vascular interstitium. We showed that in vivo generated macrophage foam cells produce superoxide, nitric oxide, and hydrogen peroxide after isolation from hypercholesterolemic rabbits. Effects of these reactive oxygens and that of peroxynitrite, likely to result from simultaneous production of nitric oxide and superoxide, were tested in vitro using metalloproteinases secreted by cultured human vascular smooth muscle cells. Enzymes in culture media or affinity-purified (pro-MMP-2 and MMP-9) were examined by SDS-PAGE zymography, Western blotting, and enzymatic assays. Under the conditions used, incubation with xanthine/xanthine oxidase increased the amount of active gelatinases, while nitric oxide donors had no noticeable effect. Incubation with peroxynitrite resulted in nitration of MMP-2 and endowed it with collagenolytic activity. Hydrogen peroxide treatment showed a catalase-reversible biphasic effect (gelatinase activation at concentrations of 4 microM, inhibition at > or = 10-50 microM). Thus, reactive oxygen species can modulate matrix degradation in areas of high oxidant stress and could therefore contribute to instability of atherosclerotic plaques.     

Intraoperative portal vein blood flow predicts allograft and patient survival following liver transplantation

Background:

We hypothesized that operative variables might predict survival following liver transplantation.

Methods:

We examined perioperative variables from 469 liver transplants carried out at the University of Washington during 2003–2006. Logistic regression determined the variables'' contributions to survival at 30, 90 and 365 days.

Results:

Portal vein blood flow (>1 l/min) was significant to patient survival at 30, 90 and 365 days. Complete reperfusion was only a significant predictor of survival at 30 days. This provided model receiver operating characteristic (ROC) area under the curve (AUC) statistics of 0.93 and 0.87 for 30 and 90 days, respectively. At 365 days, hepatic artery blood flow (>250 ml/min) combined with portal vein blood flow was significantly predictive of survival, with an AUC of 0.74. A subset analysis of 110 transplants demonstrated improved 1-year survival with more aggressive vascular revisions.

Discussion:

Portal vein blood flow is a significant predictor of survival after liver transplantation. Initially, the liver''s survival is based on portal vein blood flow; however, subsequent biliary problems and patient demise result from both poor portal vein and inadequate hepatic artery blood flow.     

Telmisartan effects on insulin resistance in obese or overweight adults without diabetes or hypertension

Angiotensin receptor blockers (ARBs) are antihypertensive agents associated with reduced risk of new-onset diabetes mellitus. The ARB telmisartan is a partial agonist of peroxisome proliferator-activated receptor-gamma (PPAR-γ). This study evaluated the effect of telmisartan on insulin resistance, a known target of PPAR-γ agonism. Overweight/obese persons with body mass index ≥28 kg/m2, waist circumference≥35 inches, and components of the metabolic syndrome without hypertension or diabetes who were not preselected for insulin resistance were enrolled. Patients were randomized to telmisartan or matching placebo for 16 weeks. The primary efficacy measure was changed from baseline in the insulin sensitivity index (SI), calculated from oral glucose tolerance testing. SI was also evaluated in a subset of patients using a hyperinsulinemic euglycemic clamp. Secondary end points included measures of insulin sensitivity and glucose and lipid metabolism. A total of 138 patients were randomized and received ≥1 dose of study medication; 128 completed the study. At end point, no significant difference was found between telmisartan and placebo groups regarding change from baseline in SI or in glucose area under the curve. No significant between-group differences were found regarding glucose metabolism or lipoprotein levels. In the population with abdominal obesity and components of the metabolic syndrome, telmisartan did not increase insulin sensitivity.     

In vitro antiplasmodial activity of ethanolic extracts of seaweed macroalgae against <Emphasis Type="Italic">Plasmodium falciparum</Emphasis>

Malaria is a major health problem in many developing countries. The drugs resistant Plasmodium falciparum causes the most virulent form of malaria in humans and it is described as a public health disaster causing increased morbidity and mortality. Thirteen seaweeds species which belong to four different families (Rhodomelaceae, Cladophoraceae, Ulvaceae, and Caulerpaceae) were collected from Mandapam coastal area and the seaweeds extracts were tested for in vitro antiplasmodial activity against P. falciparum. Among them, Caulerpa toxifolia (IC₅₀ 5.06 μg·ml⁻¹) showed potential antiplasmodial activity than other seaweeds extracts and it can be comparable with the positive control artemether (IC₅₀ 4.09 μg·ml⁻¹). Caulerpa peltata (IC₅₀ 16.69 μg·ml⁻¹) also exhibited good antiplasmodial activity and the IC₅₀ value is lesser than the positive control chloroquine (IC₅₀ 19.59 μg·ml⁻¹). Statistical analysis reveals that significant in vitro antiplasmodial activity (P < 0.05) was observed between the concentrations and time of exposure. The chemical injury to erythrocytes was also carried out and it shows that no morphological changes in erythrocytes by the ethanolic extract of seaweeds extracts after 48 h of incubation. The in vitro antiplasmodial activity might be due to the presence of sugars, proteins, and phenols in the ethanolic extracts of seaweeds. It is concluded from the present study that, the ethanolic extracts of seaweeds of C. toxifolia and C. peltata possesses lead compounds for development of antiplasmodial drugs.     

Penetrating Missile Injuries During the Iraqi Insurgency

INTRODUCTION

Since the invasion of Iraq in 2003, the conflict has evolved from asymmetric warfare to a counter-insurgency operation. This study investigates the pattern of wounding and types of injuries seen in casualties of hostile action presenting to a British military field hospital during the present conflict.

PATIENTS AND METHODS

Data were prospectively collected on 100 consecutive patients either injured or killed from hostile action from January 2006 who presented to the sole coalition field hospital in southern Iraq.

RESULTS

Eighty-two casualties presented with penetrating missile injuries from hostile action. Three subsequently died of wounds (3.7%). Forty-six (56.1%) casualties had their initial surgery performed by British military surgeons. Twenty casualties (24.4%) sustained gunshot wounds, 62 (75.6%) suffered injuries from fragmentation weapons. These 82 casualties were injured in 55 incidents (mean, 1.49 casualties; range 1–6 casualties) and sustained a total 236 wounds (mean, 2.88 wounds) affecting a mean 2.4 body regions per patient. Improvised explosive devices were responsible for a mean 2.31 casualties (range, 1–4 casualties) per incident.

CONCLUSIONS

The current insurgency in Iraq illustrates the likely evolution of modern, low-intensity, urban conflict. Improvised explosive devices employed against both military and civilian targets have become a major cause of injury. With the current global threat from terrorist bombings, both military and civilian surgeons should be aware of the spectrum and emergent management of the injuries caused by these weapons.     

Learning the lessons from conflict: Pre-hospital cervical spine stabilisation following ballistic neck trauma

Background

Current ATLS protocols dictate that spinal precautions should be in place when a casualty has sustained trauma from a significant mechanism of injury likely to damage the cervical spine. In hostile environments, the application of these precautions can place pre-hospital medical teams at considerable personal risk. It may also prevent or delay the identification of airway problems. In today's global threat from terrorism, this hostile environment is no longer restricted to conflict zones. The aim of this study was to ascertain the incidence of cervical spine injury following penetrating ballistic neck trauma in order to evaluate the need for pre-hospital cervical immobilisation in these casualties.

Methods

We retrospectively reviewed the medical records of British military casualties of combat, from Iraq and Afghanistan presenting with a penetrating neck injury during the last 5.5 years. For each patient, the mechanism of injury, neurological state on admission, medical and surgical intervention was recorded.

Results

During the study period, 90 casualties sustained a penetrating neck injury. The mechanism of injury was by explosion in 66 (73%) and from gunshot wounds in 24 (27%). Cervical spine injuries (either cervical spine fracture or cervical spinal cord injury) were present in 20 of the 90 (22%) casualties, but only 6 of these (7%) actually survived to reach hospital. Four of this six subsequently died from injuries within 72 h. Only 1 (1.8%) of the 56 survivors to reach a surgical facility sustained an unstable cervical spine injury that required surgical stabilisation. This patient later died as result of a co-existing head injury.

Conclusions

Penetrating ballistic trauma to the neck is associated with a high mortality rate. Our data suggests that it is very unlikely that penetrating ballistic trauma to the neck will result in an unstable cervical spine in survivors. In a hazardous environment (e.g. shooting incidents or terrorist bombings), the risk/benefit ratio of mandatory spinal immobilisation is unfavourable and may place medical teams at prolonged risk. In addition cervical collars may hide potential life-threatening conditions.