Trauma Victims’ Post-Operational Survival Chances Improved by Antioxidant Therapy

Many trauma patients do not survive the post-operational stage due to multiple-organ failure, but a recent study has shown that post-operational survival can be improved by antioxidant therapy.

In a study presented at the 2008 Clinical Congress of the American College of Surgeons (ACS), Bryan A. Cotton, MD, FACS, stated that “implementation of high-dose antioxidant protocol (vitamins C, E, and selenium) resulted in a reduction of pulmonary complications, in general, as well as infectious complications, including central line and catheter-related infections.”

Dr. Cotton, assistant professor of surgery at Vanderbilt University Medical Center, Nashville, TN, observed that when an abdominal wound opens up, the result is not just an infection to be treated with antibiotics. Sometimes the wounds open up, requiring reconstruction with expensive agents. Dr. Cotton observed a remarkable decrease in abdominal wall complications—including abdominal compartment syndrome and surgical site infections.

“This is a high mortality, high morbidity, may-never-return-to-work-again problem in a young healthy patient,” he said. “Abdominal wall complications are enormous, yet we noted a reduction in some of these complications with implementation of antioxidants. Importantly, the biggest difference was in those patients who had a predicted mortality exceeding 50 percent.”

Dr. Cotton and his colleagues at Vanderbilt showed that this high-dose antioxidant protocol accounted for an amazing 28% reduction in mortality in acutely injured patients. Length-of-stay, hospital and ICU, was also reduced. Dr. Cotton explained how an acute injury imposes a huge strain on the body, which releases oxygen molecules called free radicals, that cause damage at the cellular level called oxidative stress. Antioxidants work as a team in mopping up some of the oxidative stress waste byproducts, reducing the stressors that cause harm. Depletion of antioxidants is one of the mechanisms that explains why we are vulnerable. Antioxidant therapy replenishes those troops to help keep us safe.

“Antioxidant therapy is so simple and that’s what throws people off,” Dr. Cotton said. A trial conducted by Avery B. Nathens, MD, MPH, showed that some inflammatory states and responses were remarkably improved in patients who had received antioxidants versus those who did not. “Based on these results, we were inspired to initiate a study with vitamins C and E. When we looked at the literature, however, there were some concurrent studies showing that selenium had an impact too, especially on sepsis and other infectious complications. So we combined all the existing research and did a cost analysis. When we learned it would cost only $11 a patient for a seven-day course of antioxidants, we decided to give it a try.”

This retrospective study followed a total of 4,279 patients admitted to the Vanderbilt University Medical Center trauma unit during the study period. High-dose antioxidant protocol was administered to all acutely injured patients (2,258 individuals) admitted to the center between October 1, 2005, and September 30, 2006. This treatment included 1,000 mg. vitamin C (ascorbic acid) -tocopherol acetate), each routinely given everyaand 1,000 IU vitamin E (DL- eight hours by mouth, if the patient could take it that way. In addition, 200 mcg. selenium was given once daily intravenously. Patients received these supplements upon arrival, and they were continued for seven days or until discharge, whichever happened first. Patients who were pregnant or had serum creatinine levels >2.5mg/dL did not receive antioxidants.

A comparison cohort was made up of all patients (2,021 individuals) admitted to the trauma center between October 1, 2004, and September 30, 2005—prior to implementation of the antioxidant protocol. While pneumonia and renal failure were similar between the groups, the incidence of abdominal compartment syndrome was significantly less (90 versus 31), as were catheter-related infections (75 versus 50) and surgical site infections (101 versus 44). Pulmonary failure—meaning the patient could not get off the ventilator—was less as well (721 versus 528).

Dr. Cotton is now prescribing high-dose antioxidants only to the most seriously ill patients in the ICU, as they seem to derive the greatest benefit. He and his colleagues will now focus on dose adjustments and length of administration to see if the doses and duration they are currently using are optimal. They have been approached by several groups that are interested in collaborating and investigating these agents as part of multiinstitutional trials and expanding their use to critically ill nontrauma patients.

“While we are all looking for that magic bullet to cure some of the horrible things that can happen after someone is injured or has an operation, we have something at our disposal,” Dr. Cotton said. “It might not be that magic bullet, but it is a very inexpensive and safe way to reduce complications and mortality in the sickest patients.”

Assisting Dr. Cotton with this study were Aviram Giladi, BS; Bryan R. Collier, DO, FACS; Lesly A. Dossett, MD; and Sloan B. Fleming, PharmD, all from Vanderbilt. He received no funding for this research.

Scientists Finding Anti-Obesity Drugs With Fewer Side Effects

Fen-phen was once regarded as a miracle weight-loss drug, but when it induced heart valve lesions and mother life-threatening side effects, it was taken off the market. UT Southwestern Medical Center scientists are exploring Fen-phen’s behavior in the brain so that safer anti-obesity drugs with less side effects can be developed.

In a recent study, the researchers define a circuit in the brain that explains the ways fenfluramine, a component of Fen-phen, suppresses appetite.

“Our findings provide evidence that the neural circuit we’ve proposed is sufficient for the neurotransmitter serotonin to regulate food intake and body weight, ” said Dr. Joel Elmquist, professor of internal medicine and pharmacology at UT Southwestern and senior author of the study. “Fen-phen works directly on this pathway. Unfortunately, that drug also adversely affects peripheral tissue such as the heart.”

Mice were engineered for the current study, in which the expression of a serotonin receptor called 5-hydroxytryptamine 2C was blocked throughout the entire body. Previously, this produced obese mice resistant to the anorexic actions of fenfluramine. When activated by serotonin, however, this receptor is also known to suppress appetite. Using this mouse model, the authors engineered another set of mice in which the same serotonin receptor was blocked everywhere in the body except within a group of brain cells called pro-opiomelanocortin, or POMC, neurons. The POMC neurons, which are found in the hypothalamus, are also known to play an important role in suppressing appetite and inducing weight loss.

The scientists noted that the animals with no serotonin 2c receptors expectedly developed obesity as well as other metabolism disorders such as increased food intake, hyperactivity and leptin insensitivity. They also were prone to spontaneous seizures, said Dr. Elmquist. The mice in which the serotonin receptor was fre-expressed and functioning only in the POMC neurons stayed slim and responded to fenfluramine.

“The POMC-specific reactivation of the receptor only in POMC neurons normalizes the abnormal metabolism in these mice,” Dr. Elmquist said. “The animals don’t eat excessively. Their hyperactivity is also gone.”

Previous work from the UT Southwestern group led to the hypothesis that Fen-phen worked by activating the serotonin 2c receptor in the POMC neurons in the hypothalamus. The current work provides genetic proof supporting this model.

“Conventional wisdom is that fenfluramine increases serotonin release that then activates serotonin receptors in the brain to regulate food intake and body weight, but unfortunately, this drug also causes lesions in heart valves,” he said. “If you could develop a drug that would travel to both the brain and the peripheral tissues, and then give a blocker to protect the heart, it’s possible that you could prevent the harmful side effects and still aid weight loss. Admittedly, that’s a bit farfetched, but this mouse model could be used to test that theory.”

The team’s next step is to determine whether they’ve identified the sole circuit required to suppress appetite and induce weight loss.

Spotting The Difference Between Heartburn & Heart Attack Can Be A Lifesaver

How many people regret over-indulging on Thanksgiving Day? Some can sleep off the tumult in their stomachs, others experience alarming symptoms. Is that pain in their chest heartburn or a heat attack? The symptoms are similar, but the health consequences differ dramatically.

“We see people in the Emergency Room who think they are only having severe heartburn or experiencing the flu when they are actually having a heart attack,” said Nick Zenarosa, M.D., emergency medicine physician on the medical staff at Baylor University Medical Center at Dallas.

If you think you are experiencing heartburn, Dr. Zenarosa recommends watching for the following symptoms which are not typical of heartburn and could indicate a heart attack:

• Breaking into a cold sweat
• Pain moving from the chest into the jaw, shoulder or arms
• Increased pain when you exert yourself, rapid onset of fatigue
• shortness of breath
• turning pale
• slow or no response of symptoms to antacids
• nausea and possible vomiting

Keep in mind that the signs of a heart attack can be subtle, particularly in women. If you are experiencing any of these signs, coupled with chest pain and/or pain that radiates through your jaw or down your arm, be sure to go to an Emergency Room.

Time is of the essence when a person is having a heart attack. According to the National Heart, Lung and Blood Institute, the sooner clot-busting drugs and other artery-opening treatments are started, the more good they will do, and the greater the chances are for survival and a full recovery.

Infecção pelo vírus da hepatite C pode ser um fator de risco para o câncer renal

Pesquisadores do Henry Ford Hospital, de Detroit, anunciaram que a infecção crônica pelo vírus da hepatite C (HCV) parece ser um fator de risco para a ocorrência de carcinoma renal de células claras primário.O pesquisador principal, o Dr. Stuart C. Gordon declarou à Reuters Health que “o estudo iniciou quando começamos a perceber um número aparentemente grande e incomum de pacientes com câncer renal que compareciam à nossa clínica (hepatologia)”.

Este fato levou o Dr. Gordon e seus colaboradores a examinar os prontuários do Henry Ford Hospital para determinar qual a incidência de carcinoma renal de células claras entre os pacientes infectados pelo vírus da hepatite C, diagnosticados entre 1997 e 2008 e com idade superior a 18 anos. Eles foram comparados com os pacientes que apresentavam sorologia anti-HCV negativa.

A coorte era composta por 74.570 pacientes, sendo 9.401 deles com sorologia anti-HCV positiva (12,6%).

O Dr. Gordon relatou durante o encontro The Liver Meeting 2008, uma reunião anual da American Association for the Study of Liver Diseases, que ocorreram 163 casos de carcinoma renal de células claras entre os pacientes que apresentavam sorologia para o HCV negativa e 35 casos entre os pacientes com anti-HCV positivo. Isso indica uma taxa de prevalência de 0,25 e 0,37 casos de carcinoma renal de células claras a cada 100 pacientes com sorologia anti-HCV negativa e positiva, respectivamente.

Os pesquisadores observaram que “a média de idade no diagnóstico de carcinoma renal de células claras era muito menor entre os pacientes que apresentavam infecção crônica pelo HCV (52 anos versus 63 anos)”.

A odds ratio (OR) não ajustada para a ocorrência de carcinoma renal de células claras quando se compara indivíduos infectados e não infectados pelo HCV foi de 1,49. Já os homens com diagnóstico de infecção pelo HCV entre os 18 e 50 anos têm OR ajustada de 4,8 para o desenvolvimento de carcinoma renal de células claras.

Enquanto estes achados indicam uma associação entre a infecção crônica pelo HCV e o carcinoma renal, principalmente entre homens jovens, os pesquisadores ressaltam que estes resultados podem estar sendo influenciados por um viés de seleção (por se tratar de um centro terciário), assim como por outros fatores de risco que não foram aferidos.

Martha Kerr

Transplante de medula óssea com toxicidade reduzida pode curar a anemia falciforme

Os resultados de um estudo pequeno sugerem que a anemia falciforme pode ser curada com o transplante de células hematopoiéticas utilizando um esquema de condicionamento de intensidade reduzida.”O transplante de medula óssea é a única cura conhecida para a anemia falciforme. Mas os médicos têm evitado realizá-los nestes pacientes, pois as complicações de um transplante tradicional de medula óssea podem ser fatais”, o Dr. Lakshmanan Krishamurti, do Children’s Hospital of Pittsburgh, Pensilvânia, afirmou em uma declaração.

“Através da abordagem de intensidade reduzida que desenvolvemos”, acrescentou, “a possibilidade de complicações é drasticamente reduzida. Este estudo oferece uma esperança de cura para milhares de pacientes com anemia falciforme grave”.

Em seu estudo, a equipe de pesquisa avaliou os desfechos de sete pacientes submetidos ao transplante de medula óssea entre irmãos com compatibilidade HLA após receberem um regime de condicionamento de intensidade reduzida consistindo de fludarabina, busulfan, globulina antitimócitos de origem eqüina e irradiação linfóide total com proteção de pulmões, fígado, coração e gônadas no dia 1. A ciclosporina e o micofenolato mofetil foram usados para a profilaxia da doença enxerto versus hospedeiro.

Os pesquisadores relataram as suas descobertas no periódico Biology of Blood and Marrow Transplantation de novembro.

O regime de condicionamento de intensidade reduzida, observam os autores, foi bem tolerado e a recuperação hematopoiética ocorreu em todos os pacientes.

Em 2 a 8,5 anos após o transplante, seis dos pacientes apresentavam um estabelecimento estável da imunossupressão e não apresentavam nenhum sintoma relacionado com a anemia falciforme, indica o relatório.

Embora um quimerismo misto tenha sido notado nos compartimentos linfóides e mononucleares, a eritropoiese observada nos seis pacientes com enxertamento estável, era na maior parte, ou totalmente, de origem do doador.