Fighting Bacteria By Preventing Them From Talking To Each Other

Disruption of biological clocks can lead to neurodegeneration, early death, study suggests

Can we prevent the developement of antibacterial resistance?

Antibiotic resistance - Can we trace it from animal farms to the medical clinics?

The increasing incidence of hospital acquired infections with antibiotic resistant bacteria has become a major issue in the recent past. These infections due to the resistant bacteria not only increased morbidity and mortality but also increase cost of management in the hospitals. In one study from a premier medical institute in New Delhi, it was found that methicillin resistant staphylococcus bacterial infections were present in the 7.5% - 41% of cultures from these wounds from 3 different hospitals.(1).  About one quarter of healthy people carry one or more strains staphylococci asymptomatically at any given time, and infections are commonly endogenous being caused by the patient’s colonizing strain.(2). It was observed that use of antibiotics in the farm houses results in the development of resistance bacteria and it was felt this reaches the humans. Farmers regularly treat cattle, pigs, and chickens with antibiotics to dampen low-level infections that slow the growth of these animals. But wily bacteria quickly evolve resistance. Livestock farms often brim with resistant bugs that can pass to humans and potentially spread resistance to other microbes. Most farm screens have traced resistance only in pathogenic bugs—those that cause disease. But such organisms make up just a small percentage of gut microbes in pigs, The new data, he says, suggest that the common practice of using swine waste as a fertilizer is like spreading truckloads of antibiotic resistance on farmland. Those bacteria can share their resistance with other bacteria that happen to be on crops and in downstream aquatic ecosystems—bacteria that could cause illness, Chénier says. "This is a time bomb." Employees at slaughterhouses and meat-processing facilities say that they follow guidelines to keep the pigs' gut bacteria from contaminating the rest of the meat and the facility. "Risk assessment shows that by the time food gets to the consumer, there's very little resistant bacteria left in the meat".

Ecologist Martin Chénier of McGill University in Montreal, Canada, and his colleagues examined bacteria on a university farm. This farm  in January 2007 banned all antibiotics, including two commonly used varieties: tylosin and chlortetracycline. They monitored gut bacterial populations in 10 pigs by searching for bacteria resistant to common drugs in their waste.

To the team's surprise, the entire bug community kept most of its armor against the antibiotics, even after 2 ½ years. When the researchers grew the bacteria in the lab, for example, 70% to 100% of them were still resistant to chlortetracycline when the pigs were slaughtered. "I didn't expect such high levels of resistance would remain," says Chénier, whose team will publish the results in the January issue of Microbial Ecology.

References:

1) Gadepalli R et al  Clinical and molecular characteristics of nosocomial methicillin-resistant Staphylococcus aureus skin and soft tissue isolates from three Indian hospitals J Hosp Infect. 2009 Nov;73(3):253-63. Epub 2009 Sep 25.

2)  Von Eiff C, Becker K, Machka K, Stammer H, Peters G. Nasal carriage as a source of Staphylococcus aureus bacteremia. Study Group. N Engl J Med. 2001; 344:11–26.

World Diabetes Day 2011

World diabetes day 14th Nov 2011

This is going to be challenge for India and Indian women to keep diabetes under control or prevent it altogether. The epidemiological surveys are saying the Indian diet, working habits, exercise patterns, better economic conditions and their genetic constitution are favoring the early onset of diabetes. So, Indian woman has to work very hard to keep herself and her family safe from the ill effects of diabetes. - Let us see the next decade and let us prove that epidemiologists are wrong once again!!! 

Endothelial progenitor cells - Vasculogenesis

Endothelial Progenitor Cells (EPCs) are immature cells. They have the capacity to proliferate, migrate and differentiate in to endothelial lineage cells.  Hematopoietic stem cells and EPCs are derived from the common precursor (hemangioblast). These two stem cells share similar surface marker antigens. They are Flk-1, Tie-2, c-Kit, Sca-1, AC133 (CD133) and CD34+.

It was interesting to note that in 1997 Asahara et al found the importance of CD34+ cells in the neovasculogenesis.  The antigens expressed on the surface differentiate the HSCs and EPCs from the leukocyte fraction of peripheral blood. CD34+ is expressed by all the HSCs but lost by the differentiated hematopoietic cells.

It was believed that the post natal neovascularisation (angiogenesis) is possible by the proliferation, migration, remodelling of the fully differentiated endothelial cells. Vasculogenesis was considered to be formation of embryonic blood vessels from the EPCs or angioblasts. Vasculogenesis begins as a cluster formation or blood island comprising angioblasts at the periphery and HSCs at the center. So, demonstration of HSCs and EPCs in the peripheral blood based on the surface antigens on them proves the fact that there are stem cells circulating in peripheral blood and they are involved in the neovasculogenesis. A potentially limiting factor in strategies designed to promote neovascularisation of ischemic tissues is the resident population of ECs, that is competent to respond to administered angiogenic cytokines.

Asahara et al felt that this issue may be successfully addressed with autologous EC transplants. The fact that progenitor ECs home to foci of angiogenesis suggests potential utility as autologous vectors for gene therapy. For antineoplastic therapies, MBCD34+ cells could be transfected with or coupled to antitumor drugs or angiogenesis inhibitors. For treatment of regional ischemia, angiogenesis could be amplified by transfection of MBCD34+ cells to achieve constitutive expression of angiogenic cytokines or provisional matrix proteins or both. In a recent study by Turan et al have shown that the circulating EPCs were reduced in patients with extensive coronary artery disease (3 vessel disease / SYNTAX score >33). We may need to understand more about this fact and bring to this point from bench to the routine bed side management of patients.

References

Asahara T, Murohara T, Sullivan  A  et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997; 275:964-967

Turan RG, Turan Ch, Bozdag-Turam I et al. Impaired mobilization of CD 133+bone derived circulating progenitor cells with an increased number of diseased coronary arteries in ischemic heart disease patients with diabetes. Circ J 2011; 75:2635-2641 

Injuries in patients who are on oral anticoagulants and antiplatelet drugs

Injuries in patients who are on oral anticoagulants and antiplatelet drugs

In the recent past increasing number of cardiovascular patients (atrial fibrillation, DVT, post interventions) are put on oral anticoagulants and antiplatelet drugs after a life or limb threatening cardiovascular event.  Therapeutic advancements are increasing probably the need for these special classes of drugs in our patients. We are concerned about the risk of bleeding in such patients.  Spontaneous bleeding is one and prolonged and profuse bleeding from trauma is the other which we may have address in some of these patients. We have already noted the increased risk of puncture site complications (bleeding, pseudo-aneurysm) after angiogram or angioplasty in those receiving the triple antiplatelet therapy in the cardiac patients.  The patients are leading active lives and traveling like any person after recovering from cardiovascular events and there is a probability that they may be prone for injuries. 

If a patient who is on oral anticoagulants or antiplatelet drugs sustain injuries there can be more bleeding and some times it can be life threatening. Bleeding in to the closed cavities such as intracranial, intra thoracic and retroperitoneal can continue for longer periods under the influence of the drugs.  Recently DJ Bonville et al from Albany retrospectively reviewed (3,436) the impact of pre-injury warfarin and antiplatelet drugs (456) on the outcomes of trauma patients from 2004 – 2007 at a New York state level-1 trauma center.   Patients on Warfarin were 3.1 times more likely die after adjusting for potential confounders. Aspirin and clopidogrel were not associated with increased mortality. But these drugs were associated with increased risk of Intra cranial hemorrhage (ICH).   But among the ICH patients increased mortality was associated with warfarin. (Surgery 2011;150: 861-8)

In many countries and in India the aging population is going increase in the coming years. In USA people above 65 years are 13% and they are going to become 20%  in 2050. Some of these are going to receive these medications.  Many studies in the past linked the mortality and morbidity of trauma patients to the use of anticoagulants. In one retrospective study Dossett  et al reviewed one million trauma patients admitted in 402 centers. In this group 36,270 patients were taking warfarin.  Among these taking warfarin 9.3% died and only 4.3% died in the group not taking warfarin. (Arch Surg 2011;146:565-70).

Initiation of oral anticoagulation after giving heparin for 5 days in DVT patients is practiced in many hospitals. The tablet warfarin action is monitored by testing the INR frequently and maintained between 2-3. It is difficult for the patients who are not living close to the towns to get the reliable INR tests. The Indian diet may be also interfering with action of the drugs. Anticoagulation clinics are not present in states like Andhra Pradesh in India. There is a need for the development of web sites to guide these patients about the drug interactions and precautions to be taken while taking the medication. It will be very convenient for the patients if is possible to provide the free testing facilities at the pharmacies supplying (selling) the medications. These patients can carry a card which can be flashed in case of emergency such as trauma to help the treating doctors to take necessary precautions and reverse the effects of anticoagulation (warfarin effect). Correction with Fresh frozen plasma, Injection Vitamin K  and Factor VIIa are used for reversing the warfarin effect.

Critical limb ischemia (PAD) what is the natural course and outcome with interventions?


PAD affects 8 to 10 million  people in America alone and is associated with a threefold to sixfold increased risk of cardiovascular morbidity and death compared with individuals without PAD.
PAD patients are at an exceptionally high risk for cardiovascular events and most eventually die of a cardiac or cerebrovascular event. Patients with CLI also have a greater risk of sustaining cardiovascular ischemic events than those with PAD alone.1 Patients with CLI represent approximately 1% of the total number of patients with PAD, with overall mortality in these patients approaching 50% at 5 years and 70% at 10 years. Immediate postoperative mortality and major limb amputation is also considerable, with a recent meta-analysis reviewing 31 studies involving bypass grafts for CLI showing rates as high as 11.6%. A study in 2009 revealed amputation rates at 1 year after lower extremity bypass of 12% for patients with CLI vs 1% for patients with claudication.The recent multicenter, randomized trial of edifoligide for the prevention of vein graft failure in lower extremity bypass surgery (PREVENT III) confers, arguably, the best data for CLI patients undergoing vein bypass grafting, because it studied strictly CLI patients and included patients with advanced co-morbidities or those requiring complex operative procedures. A 2.7% perioperative mortality rate, 5.2% graft occlusion rate, 16% mortality rate at 1 year, 80% secondary patency rate at 1 year, and an 88% limb salvage rate at 1 year was observed. Well, we vascular surgeons should remember all these facts during the treatment planning!

References


1. Criqui MH, Langer RD, Fronek A, Feigelson HS, Klauber MR, Mccann TJ, et al. Mortality Over A Period of 10 Years in Patients with Peripheral Arterial-Disease. N Engl J Med 1992;326:381-6.

2. Shammas NW. Epidemiology, classification, and modifiable risk factors of peripheral arterial disease. Vasc Health Risk Manag 2007;3:229-34.

3. Management of peripheral arterial disease (PAD). TransAtlantic InterSociety Consensus (TASC). Eur J Vasc Endovasc Surg 2000;19(Suppl A):Si-xxviii. S1-250.

4. Nehler MR, Peyton BD. Is revascularization and limb salvage always the treatment for critical limb ischemia? J Cardiovasc Surg 2004;45: 177-84.

5. Watelet J, Soury P, Menard JF, Plissonnier D, Peillon C, Lestrat JP, et al. Femoropopliteal bypass: In situ or reversed vein grafts? Ten-year results of a randomized prospective study. Ann Vasc Surg 1997;11: 510-9.

6. Albers M, Romiti M, Brochado-Neto FC, De Luccia N, Pereira CAB. Meta-analysis of popliteal-to-distal vein bypass grafts for critical ischemia. J Vasc Surg 2006;43:498-503.

7. Goodney PP, Likosky DS, Cronenwett JL. Predicting ambulation status one year after lower extremity bypass. J Vasc Surg 2009;49:1431-9.

8. Conte MS, Bandyk DF, Clowes AW, Moneta GL, Seely L, Lorenz TJ, et al. Results of PREVENT III: a multicenter, randomized trial of edifoligide for the prevention of vein graft failure in lower extremity bypass surgery. J Vasc Surg 2006;43:742-50.

9. Bertele V, Roncaglioni MC, Pangrazzi J, Terzian E, Tognoni G. Clinical outcome and its predictors in 1560 patients with critical leg ischaemia. Eur J Vasc Endovasc Surg 1999;18:401-10.

10. Brahmanandam SM, Messina LM, Belkin M, Conte MS, Nguyen LL. Determinants of hospital disposition after lower extremity bypass surgery. Presented at: Vascular Annual Meeting, Scientific Program, Jun 11-14, 2009;166-7.

11. Hunink MGM, Wong JB, Donaldson MC, Meyerovitz MF, Devries J, Harrington DP. Revascularization for femoropopliteal disease—a decision and cost-effectiveness analysis. JAMA 1995;274:165-71

Fwd: world mental health day 2011

Begin forwarded message:

From: Pinjala <pinjala@hotmail.com>

Subject: world mental health day 2011

Date: 11 October 2011 1:36:01 AM GMT+05:30

To: pinjala.vascular@blogspot.com

wMental illness is a universal malady. According to World Health Organisation's statistics for 2002, 154 million people across the globe suffer from depression. 

Read more: World Mental Health Day-2011 | MedIndia http://www.medindia.net/news/healthinfocus/World-Mental-Health-Day-2011-91692-1.htm#ixzz1aPYMXzuV

Carotid artery interventions and Outcomes

NASCET, ACAS  trials remain to be gold standards for reducing the risk of a subsequent cerebro-vascular accident. Despite several large studies the literature remains unclear about the absolute benefit of one procedure over the other. The recent data from CREST has showed increased risk of CVA among the patients undergoing CAS (4.1% vs 2.3%) and decreased risk of MI  in CAS compared with CEA ( 1.1% vs2.3%). In this study Brewster et al have studied 495  procedures performed at one institute where 14 physicians participated in 3 year study period.

A biomarker for Takayasu's disease

It was found that PTX3 levels are more accurate than CRP levels or ESR for detecting disease

 activity in selected patients with known Takayasu arteritis activity. Further studies confirming the data in a broader spectrum of patients with unknown or equivocal disease activity are needed before this marker can be used routinely as a biomarker in the clinical or research settings. Pentraxins are another possible biomarker. Pentraxins are a superfamily of proteins that are highly conserved in evolution, recognize a wide range of exogenous pathogenic substances, alter self molecules, and behave as acute-phase proteins. They are categorized as short and long pentraxins on the basis of their primary structure. C-reactive protein (CRP) and serum amyloid P are classic short pentraxins produced in the liver. Pentraxin-3 (PTX3) is a prototype of the long pentraxins. Innate immunity cells (most notably, dendritic cells and macrophages) and vascular cells produce PTX3 in response to proinflammatory signals and Toll-like receptor engagement. Pentraxin-3 plays a nonredundant role in the recognition of selected pathogens, activates the complement system, regulates cell proliferation and angiogenesis, and participates in the formation of the cumulus oophorus. This protein is synthesized locally at sites of inflammation, and increased levels are associated with vascular inflammation in different diseases affecting blood vessels; increased levels have been observed in the serum of patients with small-vessel vasculitis and in the synovial fluid of patients with rheumatoid arthritis. In future we may depending more on this marker to assess the active nature of the disease.

Longterm use of LMWH in DVT patients

Am J Med. 2011 Aug;124(8):756-65.

Long-term low-molecular-weight heparin and the post-thrombotic syndrome: a systematic review. Hull RD, Liang J, Townshend G.

Source. University of Calgary, Alberta, Canada. rdhull@ucalgary.ca

Abstract OBJECTIVE: Post-thrombotic syndrome causes considerable morbidity. The Home-LITE study showed a lower incidence of post-thrombotic syndrome and venous ulcers after 3 months of treating deep vein thrombosis with the low-molecular-weight heparin tinzaparin versus oral anticoagulation. This systematic review examined whether long-term treatment of deep vein thrombosis using low-molecular-weight heparin, rather than oral anticoagulation, reduces development of post-thrombotic syndrome. METHODS: We identified 9 articles comparing treatment of deep vein thrombosis using long-term low-molecular-weight heparin with any comparator, which reported outcomes relevant to the post-thrombotic syndrome assessed ≥ 3 months post-deep vein thrombosis. RESULTS: Pooled analysis of 2 studies yielded an 87% risk reduction with low-molecular-weight heparin in the incidence of venous ulcers at ≥ 3 months (P = .019). One study showed an overall odds ratio of 0.77 (P = .001) favoring low-molecular-weight heparin for the presence of 8 patient-reported post-thrombotic syndrome signs and symptoms. Pooled analysis of 5 studies showed a risk ratio for low-molecular-weight heparin versus oral anticoagulation of 0.66 (P < .0001) for complete recanalization of thrombosed veins.

CONCLUSION: These results support the lower incidence of post-thrombotic syndrome and venous ulcers observed in Home-LITE. Long-term treatment with low-molecular-weight heparin rather than oral anticoagulation after a deep vein thrombosis may reduce or prevent development of signs and symptoms associated with post-thrombotic syndrome. Post-thrombotic syndrome and associated acute ulcers may develop more rapidly after deep vein thrombosis than previously recognized.

PGE-1 in Peripheral arterial disease patients

Meta-analysis of randomised controlled prostaglandin E1 studies in peripheral arterial occlusive disease stages III and IV. By  Creutzig A, Lehmacher W, Elze M.

Source Angiologische Gemeinschaftspraxis und Klinik für Nieren, Hochdruck-und Gefässkrankheiten, Klinikum, Hannover. andreas@creutzig.de

Abstract

BACKGROUND:

The relevance of Prostaglandin El (PGE,) in the treatment of peripheral arterial occlusive disease stage III and IV was to be evaluated for the first time by a meta-analysis.

PATIENTS AND METHODS:

Altogether, 643 patients were analyzed from seven randomized, controlled PGE1 studies that were comparable with regard to patient selection, study design and endpoints. Of these, only placebo-controlled studies (n = 254) were included in the formal meta-analysis using the method of DerSimonian and Laird. Additionally, the response rate and the rate of adverse events were determined for the pooled groups of all studies.

RESULTS:

At the end of treatment, PGE1 showed a significantly better response (ulcer healing and/or pain reduction) as compared to placebo (47.8% for PGE1, vs. 25.2% for placebo, p = 0.0294). A significant difference in favor of PGE1 was also seen for the combined endpoint "major amputation or death" after 6-month follow-up (22.6% for PGE1 vs. 36.2% for placebo, p = 0.0150). The response rate (ulcer healing and/or pain relief) of the pooled treatment groups was 60.2% for PGE1, 25.2% for placebo, and 53.6% for iloprost. The adverse events rate of the pooled treatment groups showed good tolerability for PGE, with a rate of 39.6% in comparison to 73.9% for iloprost and 15.4% for placebo.

CONCLUSION:

For patients with peripheral arterial occlusive disease stage III or IV not eligible for arterial reconstruction, PGE1 therapy not only has significant beneficial effects over placebo on ulcer healing and pain relief but also increases the rate of patients surviving with both legs after 6-months follow-up.

Ref : http://www.ncbi.nlm.nih.gov/pubmed/15461065

Collateral blood supply determines outcome?

'Back-Up System' Reduces Heart Disease Deaths, Research Finds 

For many years, doctors believed that there were no connections between the main coronary arteries, and if one of these arteries got blocked patients would normally undergo bypass surgery or stenting. However, research is now building up concerning the importance of coronary collaterals. A study pooled data from 12 studies enrolling 6,529 patients. Researchers compared patient survival rates in participants with a high number of natural bypass vessels with those with minimal bypass vessels. Survival rates were higher among those who had a higher number of well developed vessels, compared to those with fewer or no such vessels. It is not yet clear why some people have better bypass networks than others, but scientists believe genes and lifestyle factors play an important role.

Ref:  http://www.sciencedaily.com/releases/2011/09/110929235159.htm

Myocardial infarction without evidence of obstruction in Coronary angiogram 

A substantial proportion of patients with myocardial infarction (MI) have no angiographically obstructive (≥50% diameter stenosis) coronary artery disease (CAD), including ≈7% to 32% of women and 6% to 12% of men. Plaque rupture and ulceration are common in women with myocardial infarction without angiographically demonstrable obstructive coronary artery disease. Vasospasm and embolism are possible mechanisms without plaque disruption. Intravascular ultrasound and cardiac magnetic resonance imaging provide complementary mechanistic insights into female myocardial infarction patients without obstructive coronary artery disease and may be useful in identifying potential causes and therapies.
http://circ.ahajournals.org/content/124/13/1414.abstract

Gila monsters are known to us as they secrete the incretins in their saliva.
But in this issue of JCI - the cover page is gila monster , Mast cells battle Gila monster venom
Heloderma suspectum, also known as the venomous Gila monster lizard. In this issue, Akahoshi and colleagues investigated whether mast cells can enhance resistance to the venom of the Gila monster (page 4180). Using two types of mast cell–deficient mice as well as mice selectively lacking mast cell–derived protease activities, the authors found that mast cells can enhance host resistance to the toxicity of Gila monster venom and can reduce the morbidity and mortality induced by venoms from two species of scorpions.

More intracranial in carotid artery angioplasty patients!

Intracranial hemorrhage risk is higher after carotid artery Angioplasty and stenting in Symptomatic patients!

Intra cranial hemorrhage after carotid artery endarterectomy or carotid artery angioplasty and stenting is a serious complication. It is considered to be associated with cerebral hyper perfusion. Blood pressure in the peri procedural period is very important to avoid this complication. There seems to be 30 fold increased risk of mortality before discharge if there is intracranial hemorrhage. Symptomatic presentations and carotid artery angioplasty and stenting are associated with 6 fold to 7 fold increased risk of intracranial hemorrhage when compared to the carotid endarterectomy. This point needs attention when we consider carotid artery angioplasty stenting in symptomatic patients!!!

Ref: http://stroke.ahajournals.org/content/42/10/2782.abstract