DRESS Syndrome

Allopurinol is a drug used primarily to treat hyperuricemia and its complications, including chronic gout.  The Drug Rash with Eosinophilia and Systemic Symptom (DRESS) is a severe adverse drug-induced reaction. It is a syndrome, caused by exposure to certain medications that may cause a rash, fever, inflammation of internal organs, lymphadenopathy, and characteristic hematologic abnormalities such as eosinophilia, thrombocytopenia, and atypical lymphocytosis. Allopurinol can cause DRESS syndrome in 2-6 weeks after allopurinol therapy.  In this text, we present a patient with complaints of fever, jaundice, dyspnea, and generalized rash after 3 months of allopurinol treatment for gout.

A 70-year-old man was admitted to another hospital with arthralgia and was diagnosed as gout; thus, he was prescribed allopurinol treatment. He was admitted to our clinic with complaints of fever, jaundice, dyspnea, and generalized rash after 3 months of allopurinol treatment for gout The patient had chronic renal failure and hypertension. There was no history of asthma or rash, nor any known allergies. Family history was unremarkable. Physical examination detected fever (38.5°C), jaundice, diffuse erythema and maculo-papular rash all over the body. Analysis of blood revealed the following: Hemoglobin, 10.1 g/dl; WBC, 19000/mm ³ ; platelet, 326000/mm ³ ; eosinophil, 7300/mm ³ ; Alanine Transaminase (ALT), 429 IU/L; Aspartate Aminotransferase (AST), 369 IU/L; Gamma-Glutamyl Transpeptidase (GGT), 481 IU/L; Alkaline Phosphatase (ALP), 773 IU/L; Lactate Dehydrogenase (LDH), 721 IU/L; urea, 76 mg/dl; creatinine, 2.1 mg/dl; uric acid, 4 mg/ dl; International Normalized Ratio (INR), 1.4; total bilirubin, 16.9 mg/dl; direct bilirubin, 8 mg/dl; and IgE, 574 IU/ ml. No immature eosinophils were observed in the peripheral blood smear. Complete urinalysis was normal. Blood and urine cultures were sterile. Hepatitis B Surface Antigen (HBsAg), IgM Antibody to Hepatitis B Core Antigen (anti-HBcIgM), Antibody to Hepatitis C Virus (anti-HCV), IgM antibody for Hepatitis A Virus (anti-HAV IgM), Anti-Cytomegalovirus IgM Antibody (anti-CMV IgM), and anti-toxoplasma IgM were negative.  Brucella  agglutination test showed negative result. Anti-Nuclear Antibodies (ANA), Anti-Mitochondria Antibody (AMA), and Anti-Smooth Muscle Antibody (SMA) were negative. Abdominal ultrasonography showed a normal liver size, grade-2 hepatosteatosis and sludge in the lumen of the gallbladder. Endoscopic Retrograde Cholangiopancreatography (ERCP) was performed to rule out mechanical icterus and was found normal. Transthoracic echocardiography showed normal left ventricular systolic function and ejection fraction was 67%. Skin biopsy was consistent with the clinical suspicion of drug-induced hypersensitivity. The case was diagnosed as DRESS syndrome. Allopurinol was stopped and steroid treatment initiated. Urea, creatinine, and liver enzymes were gradually elevated during the follow-up. Acute renal failure and acute liver failure were detected. Hemodialysis was performed for renal failure. Clinical status of the patient was gradually deteriorated. On day 24 of admission, the patient died because of DRESS.

Prevelance of hyperuricemia is 5%. Allopurinol is efficacious and safe in most patients, but intolerance is estimated to occur in up to 10% of treated patients. Severe or life-threatening allopurinol Adverse Reactions (AE) occur less frequently. 

DRESS syndrome is a severe adverse drug-induced reaction. It is a syndrome, caused by exposure to certain medications, which may cause a rash, fever, inflammation of internal organs, lymphadenopathy, and characteristic hematologic abnormalities such as eosinophilia, thrombocytopenia, and atypical lymphocytosis. DRESS is an acute, severe, and life-threatening disease, whose clinical presentation is unlike that of common drug hypersensitivity reactions. It involves multiorgan failure as a result of conditions such as nephritis, hepatitis, and encephalitis. Liver involvement and eosinophilia generally begin 2-6 weeks after the first drug is administered, that is, later than the skin reactions. Peripheral eosinophilia is a common finding in DRESS. Rash and hepatitis may persist for several weeks after the drug is discontinued and may be life-threatening. Diagnosisis based on clinical and laboratory findings.

The most common drugs known to cause DRESS syndrome are phenytoin, phenobarbital and carbamazepine. Allopurinol, sulphasalazine, nevirapine, and penicillamine are other such drugs. In a study of 38 patients with DRESS syndrome, all opurinol was found to be responsible for 5.3% of the cases. 

The pathogenesis of DRESS syndrome is not fully understood. Although the pathophysiology is still unknown, different factors have been postulated in DRESS syndrome's etiology. Immunological factors, genetic factors, and human herpes virus-type 6 are also implicated. A possible mechanism may be allopurinol or oxipurinol (major metabolite of allopurinol) hypersensitivity, and immune complex storage, which may result in vasculitis. Immunological factors, genetic factors, and Human Herpes Virus-type 6 are also implicated. 

There is no standard treatment of DRESS syndrome. The first step in treatment is discontinuation of the suspected drugs. High-dose corticosteroids can provide a dramatic improvement in clinical condition.  Early cessation of the drug implicated in the development of DRESS syndrome will result in a better outcome. The DRESS syndrome can cause life-threatening multi-organ failure.  The syndrome has a mortality rate of 10%. 

The patient in this case was admitted to our clinic with complaints of fever, jaundice, dyspnea, and generalized rash after 3 months of allopurinol treatment for gout. Leukocytosis, eosinophilia, elevation of liver enzymes, and hyperbilirubinemia were detected. Blood and urine cultures were sterile. HBsAg, anti-HBcIgM, anti-HCV, anti-HAV IgM, anti-CMV IgM, and anti-toxoplasma IgM were negative. Brucella agglutination test was negative. The ANA, AMA, and SMA were negative. ERCP was normal. Transthoracic echocardiography showed normal left ventricular systolic function and ejection fraction was 67%. The absence of immature eosinophils in the peripheral blood smear makes the diagnosis of eosinophilic leukemia unlikely. Other factors of renal failure and hepatitis (autoimmunity, infections, congestive heart failure, mechanical icterus) were ruled out. Skin biopsy was consistent with drug-induced hypersensitivity. DRESS syndrome was diagnosed with these clinical and laboratory findings. Thereafter, allopurinol treatment was stopped and steroid treatment was initiated. Urea, creatinine and liver enzymes were gradually elevated during the follow-up. Acute renal failure and transaminitis were detected. Hemodialysis was performed for the treatment of renal failure. Clinical status of the patient gradually deteriorated and on the 24^th day of admission, he died because of DRESS multipleorganfailure.

The DRESS syndrome is a severe adverse drug reaction and has high mortality rates. It warrants initiation of an early treatment. Drug use must be investigated in patients with complaints of fever, jaundice, generalized rash, acute renal failure, and acute liver failure in order to rule out the possibility of DRESS syndrome. Furthermore, judicious use of allopurinol may decrease the incidence and morbidity caused by this syndrome.

special drug delivery system

SPECIAL DRUG DELIVERY SYSTEM

Ocuserts – Thin elliptical microunits  e.g  pilocarpine ocuserts

Progetagerts – I/U contraceptive device

Transdermal patch  e.g  hyoscine, GTN,  fentanyl, nicotine

Prodrug  -  e.g levodopa

Liposomes

ž  Small artificial vesicles of spherical shape that can be produced from natural nontoxic phospholipids  & cholesterol.

ž  Because of their small size, hydrophilic & hydrophobic character as well as biocompatibility,

                                --promising  system for drug delivery.

Based on their size and number of bilayers.   

•       Small unilamellar vesicles

•       Large unilamellar vesicles

•       Multilamellar vesicles

                Bilayer component determine the rigidity and charge of bilayer.

      Depending on charge there are two types  of

         liposomes, cationic and anionic liposomes

Lipid formulations of AMB have been  produced

•       Liposomal amphotericin B -- consist of 10% AMB incorporated in uniform sized (60-80nm) unilammelar liposomes made up of lecithin

•       Liposome mediated cytotoxic drug delivery e.g.doxorubicin, cisplatin

•       Gene delivery for CFTR in cystic fibrosis.

ž  polymeric  nanoparticles

•       Biodegradable polymers

•       Because of their small size, can penetrate through smaller capillaries can be taken up by cells,   which allow efficient drug accumulation at the target sites.

•       Nanocapsules could perform like miniature man- made viruses, but they will release a pharmaceutical within the target cell, instead of delivering nucleic acid upon penetration of the cell membrane

Computerised minature pump – e.g   insulin,GnRH

Monoclonal antibody as drug carriers–   trastuzumab, rituximab

Zydus  -- mouth desolving tablet – e.g antiemetic drug

GENE THERAPY

                Introduction of functional genetic material into target cells to replace or supplement  defective genes, or to modify target cells so as to achieve therapeutic goals

Smoking vaccine fails clinical trials, $4.1 million in taxpayer dollars down the drain

An experimental new anti-smoking vaccine has failed miserably in clinical trials, faring no better than a placebo shot at helping people to quit smoking.

Produced in partnership with drug giant GlaxoSmithKline (GSK), Nabi Biopharmaceuticals' NicVAX was intended to help people quit smoking by triggering the production of antibodies that would attach to nicotine and prevent the substance from reaching the brain -- but the vaccine has proven to be nothing but non helpful medicine.

According to reports, the yearlong study involved 1,000 people that were given either NicVAX or a placebo shot, and who were tracked to observe smoking habits following treatment. Roughly 11 percent of patients who received the NicVAX shot quit smoking, but the same amount from the placebo group also quit smoking -- in other words, there was no difference at all in quit rates between the two groups.

Upon news of the failed Phase III trial, Nabi's stock price dropped a massive 70 percent, and GSK's dropped about one percent. But what is even more shocking is the fact that Nabi had used $4.1 million in taxpayer dollars to fund research for NicVAX. The company's website openly discloses that the US National Institute on Drug Abuse (NIDA) had granted $4.1 million in funding to the company back in 2005 for the project.

Remember, both Nabi and GSK are private, for-profit drug companies, and GSK had a net income in 2010 of nearly $3 billion. And yet the US government decided to take Americans' hard earned money and funnel it into a failed project that, if eventually "successful" (at least in terms of somehow gaining FDA approval, not in terms of actually working to "cure" smoking), will translate into $500 million in profits for Nabi, and possibly even more for GSK.

Be a Clinical Research Professional- Study from the Comfort of Your Home

An excellent opportunity for medical professionals and life sciences graduates to have a future in Clinical Research. The world needs Clinical Researchers to ensure a disease free healthy future for the people of our world. Be a Clinical Research Professional and contribute to the development of new medicines to combat diseases.

Anovus Institute of Clinical Research, located in Chandigarh, India, is a premier institute providing Masters and Diploma Courses in Clinical Research. Now Anovus offers Certificate Courses in Clinical Research from a UGC Recognized Government University.

PCCR - Professional Certificate in Clinical Research for Medical Professionals

CPCR- Certificate Programme in Clinical Research for Life Science Graduates.

These Certificate courses provide high quality courseware prepared by seasoned academicians with inputs and validation by Top-notch industry professionals.

Now you can get a UGC recognized University’s Certificate in Clinical Research in 3 months with study from home comfort.

This certificate programme equips you to enter highly regulated and technology driven field of Clinical Research and contribute to society by development of new, effective and safe drugs.

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How job seekers can overcome phone interviews easily??

Phone interviews are becoming a common way for employers to screen potential employees during the hiring process. Unlike traditional, in-person job interviews, phone interviews are usually fairly short, require less preparation, and can even be outsourced by the employer if necessary. These features make phone interviewing an effective way to narrow down the list of candidates before scheduling in-person interviews. Unfortunately, many people are not comfortable conducting a conversation of that importance over the phone. If the prospect of a phone interview makes you nervous, these tips can help turn an awkward interview into a confidence-inspiring success.

Preparation is the Name of the Game
When preparing for a phone interview, don’t forget that not all recruiters and employers schedule them ahead of time. At any moment, a recruiter could stumble across your resume or an employer could decide to call you in regards to a recent application. Your chances for success in your job search will be greatly improved if you try to always expect the unexpected (especiallyduring a job interview).

Keep Your Resume Near the Phone
Knowing that you could get a call from a recruiter or an employer at any moment, you should always keep a recent copy of your resume near the phone. That way, whether or not your phone interview is anticipated, you will have all the information you need right at your fingertips. Of course for a job interview, your resume is not the only resource you should keep handy.

Create a log for keeping track of the resumes you send out, recording each company, position title, contact name, date the position was applied for, and qualifications for the job. If you have a chance to research the company, make a file with that information, and keep it near the phone as well. Finally, you should always have access to a notepad and pen during a phone interview, so that you can write down the interviewer’s name, key questions he or she asked, and your responses.

Practice (and a Cheat Sheet) Makes Perfect
Just like with a traditional job interview, you should try to anticipate questions the interviewer might ask. If you have come up with examples and practiced your answers ahead of time, you will sound much more intelligent and confident in the interview. Moreover, since the interviewer cannot see you, there is nothing to stop you from referring to a “cheat sheet” – notes to help you remember your practiced answers, so that you never sound like you have been taken off guard.

When you practice your answers and put together your cheat sheet, you should think about job interview questions that are traditionally asked, such as:

• Tell me about yourself.
• What are your strengths and weaknesses?
• Where do you see yourself in 1/5/10 years?
• What is your leadership style? Please give an example of a real situation.
• Describe a situation where you had to work with others to solve a problem.
• Give me an example of a stressful situation you have encountered on the job. How did you handle it?
• Tell me about your three greatest accomplishments in your career.
• Do you have any questions?

Many of these questions are difficult to answer on the spot. By preparing your answers ahead of time, you give yourself the opportunity to think through your answers carefully. Your notes will refresh your memory if you draw a blank, and help prevent you from freezing up during the interview.

Giving a Fabulous Phone Interview
If you’ve done your homework, the phone interview itself should be a breeze. The important thing at this point is to remember to make sure the interviewer can hear and understand you – and vice versa – as well as possible. During the phone interview, you should:

• Find a quiet place. Children, pets, televisions, and radios are all noisy distractions that should be avoided. If the phone interview is scheduled in advance, you can arrange to have a quiet room all to yourself. If you receive the phone call unexpectedly, retreat into a quiet room or suggest another time for the interview.

• Sip water periodically. Nervousness often causes your mouth to dry out, which can in turn change the way your voice and pronunciation sounds to the interviewer. If you know about the phone interview ahead of time, you can have a glass of water on hand, along with the other materials you have prepared.

• Avoid eating, smoking, or chewing gum. Excess movement of your mouth and throat will make you harder to understand, and possibly distract or even irritate the interviewer.

• Give short answers. Many people talk too much when they are nervous. This is especially easy to do in a phone interview, because you don’t have the other person’s visual cues to indicate when it’s their turn to talk. To make sure you don’t make this mistake, only talk long enough to answer the question. A moment of silence, while it might seem awkward to you, lets the interviewer know that you are done.

Speak slowly and clearly. Speaking too fast, whether out of nervousness or habit, will hurt your chances by making you harder to understand. Instead, make a conscious effort to slow down and enunciate clearly.

• Stand, stretch, or pace occasionally. Standing improves the quality of your voice by increasing airflow to your lungs. Additionally, many people find it easier to adopt a salesperson-like attitude when they are standing or moving around. As a result, changing your posture occasionally can make you sound more confident to the interviewer.

• Smile. Believe it or not, a smile changes the quality of your voice. If you are smiling, the interviewer will hear it in your tone!

Finishing Your Phone Interview on the Right Foot

The phone interview is drawing to a close; what do you do now? These final moments are just as important as the preparation and the interview itself, as they can determine what comes next.

• Thank the interviewer. Verbally thank the interviewer for taking the time to speak with you. If you don’t remember his or her name, ask for it again and write it down, so that you can send a thank-you note as well.

• Suggest an in-person interview. The whole point of the phone interview was to score a traditional job interview, so if the interviewer doesn’t mention what will happen next, you should bring it up. For example, you can say, “Thank you very much for taking the time to call me. I’d like to have the opportunity to meet in person. When will you be scheduling the next round of interviews?”

• Reiterate your interest in the position. You want to leave the interviewer with the impression that you are enthusiastic about the job. Let him or her know how excited you are about the prospect of working with the company.

• Send a thank-you note. Just as with a traditional job interview, you should follow up with a polite thank-you note. You can also use the thank-you note to reiterate your interest in scheduling an in-person interview. Just be sure to send the thank-you note out promptly, as the interviewer may soon be making final decisions about who to call back!

Many people find a phone interview more nerve-wracking than a traditional job interview. This doesn’t have to be the case, however. While some phone interviews happen with little or no warning, in most cases you have just as much time to prepare as you would ordinarily, with the added benefit of being able to use your notes during the interview.

CMA Award of Excellence in Education for Anovus

The region´s premier educational institute, Anovus Institute of Clinical Research, has been honoured with the "Award of Excellence in Education" for 2010.

At the management meet of Chandigarh Management Association (CMA) held at Hotel Mountview, chief guest and the keynote speaker on the occasion, renowned multifaceted personality and Member of Parliament, Mr. Navjot Singh Sidhu, handed over the award to Dr. Dharinder Tayal, founder director of Anovus.

Anovus received the recognition for its innovative programme in clinical research that fulfils the much needed gap that existed in the region which opens up newer employment opportunities for the life-sciences graduates.

Dr. Dharinder Tayal was elated on receiving the honour, and said that Anovus is gradually building an ecosystem in the clinical trials domain in the region by partnering with various stakeholders, including hospitals, research organizations, clinical research organizations, academicians and institutes engaged in life sciences, etc.

Anovus is the only institute north of Delhi which provides M.Sc. in Clinical Resarch, besides one-year and two-year diploma programmes.

New Treatment to cure Uterine Cancer

A new class of experimental cancer drugs could be a potential alternative to standard chemotherapy for women with advanced endometrial or uterine cancer.

Researchers from London's Institute of Cancer Research (ICR) found that drugs known as PARP inhibitors were able to kill off endometrial cancer cells in lab dishes and said their findings should now progress into tests on human patients.

Several large drugmakers, including Abbott, Merck, Pfizer, Sanofi-Aventis and AstraZeneca, are developing PARP inhibitors, which work by blocking DNA repair mechanisms in cancer cells, stalling the cell cycle and leading to cell death.

AstraZeneca's experimental PARP drug Olaparib and Sanofi's BSI-201 are the furthest ahead in development, and results of Sanofi's drug in breast cancer showed this week that it helped women with an aggressive form of the disease live an average of almost five months longer.

PARP is short for "poly (ADP-ribose) polymerase," which is used by cancer cells to repair DNA damage. By blocking the enzyme, the drug is designed to undermine the ability of cancer cells to heal themselves.

The deletion of a gene called PTEN is key to how PARP inhibitors work and around 80 percent of cases of a common type of cancer of the uterus have this gene mutation.

"PTEN is like a predictive marker for tumors that benefit from PARP inhibition and given that around 80 percent of these cancers have PTEN gene mutation ... it would be very interesting to test this finding in clinical trials."

According to the U.S. National Cancer Institute (NCI), uterine cancer, which usually occurs after menopause, is the most common type of gynecologic cancer in the United States. This year, it is estimated that more than 43,000 women will be diagnosed with it, and almost 8,000 will die of it.