Thursday, June 24, 2010

Editorial

The next issue of Capsule is out with a greater zeal and earnestness to share the clinical experiences of our faculty members. The medical problems of the developing nations are of different nature than that of the developed ones: despite the efforts by leaders of the political and medical fields to bridge the differences. These differences obviously get reflected in the focus of medical research and the resources earmarked for the areas of interests. It may not be an exaggeration that, there is apathy in medical research towards organo phosphorus compound toxicity, which is a major global health problem with more than 200,000 deaths every year. These whopping numbers succumbing to the avoidable disaster requires immediate attention by the medical researchers in developing more effective antidote and arriving at a consensus on a standard of therapy to tranquil the controversy ridden murky waters of oxime therapy.

Capsule features an unusual case of Intravenous Intoxication of Organophosphate Compound and also an interesting case of insulinoma. Addition to the regular features a medical cross word comes to lighten the busy schedule of the physicians. The online version http://jsscapsule.blogspot.com has roused interests of a good lot, but we look forward for your valuable feedbacks to make your CAPSULE much palatable.

With best regards

Dr. Sudharshana Murthy K.A.

Professor & Head, Dept of Medicine

JSSMC & Hospital, Mysore

Dr. Narahari .M.G

Assistant Professor

JSSMC & Hospital, Mysore

Photographs



















1. Release of CAPSULE by Dr.Prem Pais, Dean & Professor Medicine, St.Johns National Academy of Health Sciences, during Medicine Update 2010. Dr.Basavana Gowdappa,Principal,JSSMC,Dr.B.V.Rajagopal,Dr.C.D.SreenivasaMurthy, Dr.K.A.Sudharshanamurthy,Professor & Head Medicine, JSSMC ,Dr.Javeed Nayeem (R-L)






















2. Felicitations to Dr.Basavana Gowdappa, Principal & Professor at Medicine Update 2010 by Sri.K.B.Ganapathi, Editor Star of Mysore




















3. Guest lecture by Dr.K.A.Sudharashanamurthy, Professor & Head Medicine, JSSMC at Medicine Update 2010, MPMRT Mysore

An Unusual Case of Intravenous Intoxication of Organophosphate Compound

Y. S. Ravikumar,K. M Srinath,L. S Adarsh, Ashik K Sasidharan, Nagalakshmi, Akash Medicine VI Unit, JSSMC & Hospital, Mysore.

A 29 year old male, a chronic alcoholic and smoker, with history of previous suicidal attempts and repeated head injuries, reported to emergency department with vague chest discomfort, incessant vomiting and severe pain in left upper and lower limbs of one day duration. Patient was irritable and slightly restless. His pulse was 100/min and regular. BP was 120/80 mmHg. Systemic examination was unremarkable and pupils were normal. ECG was normal. A provisional diagnosis of chronic alcoholism with alcoholic gastropathy and delirium tremens (DT) was considered. Psychiatrist also concurred with the diagnosis of DT. He was treated with PPIs, thiamine and IV fluids. There was no history suggestive of poisoning. However, naso-gastric aspiration was done, which was normal.

His general condition worsened over the next few hours. He developed fever, increased tracheobronchial secretions and started to desaturate. His pupils became constricted. He was immediately intubated and put on ventilator. Possibilities of brain stem encephalitis, pontine hemorrhage and organophosphate compound poisoning were considered.

The serum cholinesterase level was significantly low (730U/l). He was then started on atropine and pralidoxime. There was no history of poisoning forthcoming on repeated enquiries with the family members. His serum cholinesterase level continued to be low on the subsequent days.

Two days after admission, he developed blebs over his left upper limb, which progressed to cellulitis. Surgical opinion was taken and incision and drainage was done. Over the next two weeks his general condition improved and he was weaned off the ventilator. Patient denied having taken organophosphate compound in any form. However, his brother recollected that, he had found a syringe in the patient’s pocket while shifting him to the hospital. Patient was discharged after a few days. During follow up, he was stable and his serum cholinesterase had improved.

Clinical features like pin point pupils, increased tracheobronchial secretions supported by low serum cholinesterase levels and patient having developed cellulitis of left upper limb and RT aspiration being normal, prompted the diagnosis of organophosphate poisoning-by non-enteral route.

The other causes of low serum cholinesterase levels like, chronic anemia, malnutrition, surgical shock, blood dyscrasias, radiation, exposure to phenothiazines, uremia, chronic liver disease and malignant states, were excluded in this case. Decreased cholinesterase levels, which can be familial was excluded by checking cholinesterase levels of the patient’s siblings and mother. Hence this was a case of organophosphate compound poisoning by parenteral route. It always pays when we have a high index of suspicion in patients who are alcoholics, those with previous suicide attempts and those with some knowledge of using drugs.

Here is a brief review of mechanism of Organophosphate compound poisoning and their clinical features

Overview of Organophosphate and Carbamate toxicity
Clinical Syndromes
Acute Toxicity
Generally manifests in minutes to hours.

Evidence of cholinergic excess

SLUDGE = Salivation, Lacrimation, Urination, Defecation, Gastric Emptying

BBB = Bradycardia, Bronchorrhea, Bronchospasm

Respiratory insufficiency can result from muscle weakness, decreased central drive, increased secretions, and bronchospasm.
Intermediate Syndrome
Occurs 24-96 hours after exposure

Bulbar, respiratory, and proximal muscle weakness are prominent features

Generally resolves in 1-3 weeks
Organophosphorous Agent-Induced Delayed Peripheral Neuropathy (OPIDN)
Usually occurs several weeks after exposure

Primarily motor involvement

May resolve spontaneously, but can result in permanent neurologic dysfunction
Diagnostic Evaluation of Acute Toxicity
Atropine challenge if diagnosis is in doubt (1 mg IV in adults, 0.01-0.02 mg/kg in children)

Absence of anticholinergic signs and symptoms (tachycardia, mydriasis, decreased bowel sounds, ordry skin) strongly suggests poisoning with organophosphate or carbamate.

Decreased RBC acetylcholinesterase activity confirms diagnosis

Your browser may not support display of this image.

RBC cholinesterase less than 50% of normal indicates organophosphate toxicity.

Disadvantages of Cholinesterase as an indicator:

Normal cholinesterase level is based on population estimates and there is a wide range of distribution defining the normal levels.

False depression of RBC Cholinesterase level is seen in pernicious anemia, hemoglobinoapthies and antimalarial treatment and blood collected in oxalate tubes.

Though organophosphate poisoning is not a rare event, there are a very few case reports of parenteral OP poisoning. The report by Lyon et al. of a 24-year-old man who injected 1.8 g of malathion intravenously. In that patient serum PChE levels were undetectable for 24 hours after the injection, but the patient had only moderate toxic effects and survived. The apparent half-life of malathion, calculated from the serum concentration data, was of 2.89 hours. There are a few case reports of intramuscular and subcutaneous administration of these insecticides, where in the onset of symptoms would be delayed and persist for a longer duration warranting a longer duration of antidote therapy. An interesting case of intravenous toxicity of OP poisoning with monochrotophos who developed intermediate syndrome and required prolonged ventilation and restarting pralidoxime after the fifth day of intoxication has been reported by Badhe & Sudhakar.

These reports of parenteral intoxication of Organophosphate compound, which usually presents as a sequel of ingestion, cautions the emergency care physician to be on the watch to recognize the systemic manifestations of toxicity, actively look for signs of injection marks, local abscesses on the person. In such cases, the usual practice of gastric lavage or use of activated charcoal takes a backseat. Instead, a debridement of the local collection at the injection site would help eliminating the “depot” of insecticide

References:

1. A Case Report of Intravenous Malathion Injection with Determination of Serum Half-Life. Jack Lyon‌, Howard Taylor‌ and Bruce Ackerman‌. Clinical Toxicology 1987, Vol. 25, No. 3, Pages 243-249.

2. Intravenous organophosphate injection: an unusual way of intoxication. Güven M, Unlühizarci K, Göktaş Z, Kurtoğlu S. Hum Exp Toxicol. 1997 May; 16(5):279-80.

3. An intravenous organophosphate poisoning with intermediate syndrome: An unusual way of intoxication. Ashok Badhe, S Sudhakar Indian Journal of Critical Care Medicine 2006: 10: 3: 191-192

4. Parenteral injection of organophosphate insecticide.Apropos of two cases. Sao Paulo Med.J. vol.112 no.2 Apr/June 1994.

5. Pocket book of Pesticide Poisoning for Physicians 1st Ed- V.V.Pillay CBS Publishers.

!! PROUD MOMENTS !!

Dr.K.A.Sudharshanamurthy,Professor & Head Medicine,JSSH & MC, delivered guest lectures on Febrile Emergencies at MPMRT-Medicine Update 2010,Mysore

and Hypertensive Emergencies at Kodagu under the auspices of IMA.

Dr.Suresh Babu,M delivered guest lecture at Kodagu under the auspices of IMA.

Adjudged the best paper of the platform of State KAPICON 2010 Belagaum

A Study of Cardiac Autonomic Dysfunction in HIV/AIDS Patient

Mahesh,M, Shashidhar,Sudharshan Murthy,K.A.,Basavana Gowdappa,H

Summary

The study was designed to evaluate cardiac autonomic dysfunction in HIV/AIDS patients and its correlation withCD4 count. The study noted significant autonomic dysfunction in both HIV positive without AIDS and HIV positive with AIDS. However, there was no statistically significant correlation with the CD4 level and the presence of autonomic dysfunction.

Adjudged the best in the award paper category of the State KAPICON Belagaum

A STUDY OF GLYCEMIC INDEX OF TEN COMMON INDIAN FRUITS

Premanath,M, Basavanagowdappa,H, Mahesh, M Suresh Babu,M

Summary

The study estimated glycemic index (GI) of ten locally available fruits by an alternate method. The study also demonstrates that, GI of five of the fruits is less than 50 and diabetics can consume them in lesser quantities.

Adjudged the best presented poster of the State KAPICON Belagaum

Hepato Pulmonary Syndrome in Cryptogenic Cirrhosis of Liver - A Case Report

Mahesh .M, Sunil.R, Mohangowda, Srinivas

Interesting Case - Insulinoma

A 50 year old male presented with fatigability and increased appetite of 15 years duration. He reported that, he has to have a meal every 2 – 3 hours or else he would feel tired: tiredness would decrease after food intake. There was no history of weight loss, loose stools or palpitations. There was no history of fever, convulsions or loss of consciousness. He was not a diabetic and he gave no history of any drug intake.

Patient was of good built and afebrile. His vital parameters were stable. He had no thyromegaly, tremors or edema. Systemic examination was clinically normal. Once while the patient was symptomatic in the hospital, his glucose level was checked and was found to be less than 50mg/dl. His symptoms improved with IV dextrose.

He was then evaluated for causes of recurrent hypoglycemia. Causes like insulin or sulfonylurea intake, sepsis, cardiac, renal and hepatic failure were ruled out. He was then evaluated for Insulinoma. C peptide levels was done, which was elevated two fold. MRI abdomen was done. It showed a mass lesion at the tail of the pancreas? A possible diagnosis of Insulinoma was considered.

He was consequently put on continuous intra venous dextrose saline infusion. He is awaiting surgery now.

INSULINOMA

Insulinomas are rare pancreatic islet cell tumors (incidence of 1 case per 250,000 person-years); while most are sporadic, some are associated with the MEN1 syndrome. The characteristic clinical manifestation of an insulinoma is fasting hypoglycemia, (although some patients also have postprandial hypoglycemia), with neuroglycopenic symptoms which may or may not be preceded by sympathoadrenal (autonomic) symptoms. The neuroglycopenic symptoms of insulinoma include confusion, visual change, and unusual behavior. Sympathoadrenal symptoms may include palpitations, diaphoresis, and tremulousness. Amnesia for hypoglycemia is common. The median duration of symptoms before diagnosis was less than 1.5 years in one Mayo Clinic series. However, a few patients had probably been symptomatic for decades. As many as 20 percent of patients had been misdiagnosed with a neurological or psychiatric disorder before the insulinoma was recognized. Seizure disorder is another common misdiagnosis. Weight gain was described in 18 percent of patients. Most insulinoma are solitary and benign. Multiple insulinomas are less common, and tend to be associated with MEN1. Malignant insulinomas are also less common.

The diagnosis of insulinoma is established by demonstrating inappropriately high serum insulin concentrations during a spontaneous or induced episode of hypoglycemia (eg, 72-hour fast).

Imaging techniques are then used to localize the tumor. Accurate preoperative localization of an insulinoma is desirable. The procedures available include spiral CT, arteriography, ultrasonography (transabdominal and endoscopic), and 111-In-pentetreotide imaging. Transabdominal ultrasonography and CT are preferred initial tests, followed by endoscopic ultrasonography or arterial stimulation with hepatic venous sampling when an insulinoma has not been localized by noninvasive techniques.

There are a few disorders in which the biochemical findings simulate those of an insulinoma because they are also associated with primary overproduction of insulin:

  • Familial persistent hyperinsulinemic hypoglycemia of infancy
  • Primary islet-cell hyperplasia (also called nesidioblastosis)
  • Noninsulinoma pancreatogenous hypoglycemia syndrome
  • Post gastric bypass hypoglycemia.

The latter two conditions have the characteristic feature of producing primarily postprandial hypoglycemia.

The recommended initial treatment of patients with benign, solitary insulinoma is the surgical excision of the tumor (Grade 1A). The approach and extent of surgery should be determined based upon tumor location. Patients with multiple insulinomas (typically in the setting of MEN1), the recommended treatment is local excision of any tumors found in the head of the pancreas plus a distal subtotal pancreatectomy (Grade B). Patients with persistent hypoglycemia after surgery in whom solitary or multiple tumors are identified after additional localization procedures; a repeat operation (Grade 1A) is resorted to. In patients whom insulinoma cannot be located during pancreatic exploration, who are not candidates for or refuse surgery, diazoxide therapy for the medical management of hypoglycemia (Grade 2C) is recommended. Diazoxide (which diminishes insulin secretion and is given in divided doses of up to 1200 mg/day) sometimes used for controlling hypoglycemia. However, it can cause marked edema (which may require high doses of loop diuretics) and hirsutism.

Octreotide, an analog of somatostatin , inhibits GH secretion, but in large doses, also inhibits the secretion of TSH, insulin, and glucagon. Octreotide is highly effective in controlling the symptoms associated with glucagonomas, VIPomas, and carcinoid tumors, efficacy is less predictable for symptomatic patients with insulinoma. However, it could be a reasonable choice for patients with persistent hypoglycemia that is refractory to diazoxide. Lanreotide, another somatostatin analog is reported to have similar clinical efficacy as octreotide, and is also available in a long-acting depot form (Lanreotide-SR). Verapamil and phenytoin have also been used with some success. However, none of these drugs are as effective as tumor resection.

A patient with potentially resectable liver-isolated metastatic insulinoma, surgical resection of the hepatic metastases along with the primary tumor (Grade 1B) is the preferred option. Although the majority of cases will not be cured by surgery, given the slow-growing nature of the tumor, extended survival is sometimes possible. Other treatment options for patients with unresectable hepatic-predominant symptomatic metastatic disease include embolization, chemoembolization, radio frequency ablation, and cryoablation. The efficacy of somatostatin analogs for patients with diazoxide-refractory symptomatic hypoglycemia is unpredictable. Octreotide, as well as other systemic therapy approaches (interferon, chemotherapy, targeted radiotherapy) are tried but with variable outcomes. The traditional chemotherapy regimen of choice in malignant insulinomas has been streptozocin and doxorubicin: with objective response rates as high as 69 percent for metastatic islet cell tumors, the true radiologic response rate is probably lower, between 10 and 40 percent. Alternative regimen comprising of orally active alkylating agent temozolomide are being tried.

Novel therapeutic approaches for patients with advanced islet cell tumors include the use of targeted radiotherapy, as well as regimens incorporating inhibitors of angiogenesis, small molecule tyrosine kinase inhibitors, and inhibitors of the mammalian target of rapamycin (mTOR)

There are no evidence-based guidelines for follow-up after resection of a malignant insulinoma. Consensus-derived guidelines from the National Comprehensive Cancer Network following treatment for an islet cell tumor include:

  • Three and six months postresection — History and physical examination, tumor markers,
  • CT/MRI Long-term — History and physical examination with tumor markers every 6 to 12 months for years 1 to 3, and as clinically indicated thereafter. Imaging studies are recommended only as clinically indicated

RE-ARRANGEMENT OF COMMON MEDICAL WORDS GIVES INTERESTING RESULTS!!!

1. He burn art

Heart burn

2. Sons in Park

Parkinson’s

3. It is card

carditis

4. Far in war

Warfarin

5. It is my os

Myositis

6. An end ox

Endoxan

7. Dig it in ox

Digitoxin

8. I add sons

Addisons

9. It is mast

Mastitis

10. Did as i can is

candidiasis

Dr.M.Mahesh, Associate Professor of Medicine

Sunday, January 24, 2010

Editorial

We are happy to present the second issue of Capsule. Continuing in its earlier format we are presenting the interesting cases, activities and events of our department. This capsule features a lead article on H1N1 Influenza. Though, the media hype about Influenza has reached the ebb, the virus is taking its toll silently and the reported total death in India has reached 844, with a whopping 24,932 getting infected with the virus! Karnataka is second on list of highest reported cases of H1N1Infuenza deaths with Bangalore and Mysore cities contributing to a major share of cases! Its time again we revise our knowledge about the killer virus and equip ourselves to take up the fight! In keeping with the times and trend, we have made Capsule accessible on the web at http://jsscapsule.blogspot.com. We thank Dr. Karuturi Subrahmanyam, Post graduate student Medicine JSSMC, for maintaining the Capsule blogspot.

We intend to introduce other sections in the Capsule which would be helpful for the post graduate readers and still keep its brevity. We thank all our readers for their encouragement and welcome there suggestions and critique, which can easily be posted at the blogspot. We hope this Capsule would give you a good reading time!

With best regards

Dr.K.A.Sudharshanamurthy

Dr. Narahari, M.G

Release of Maiden Issue of Capsule



















RELEASE OF MAIDEN ISSUE OF CAPSULE BY EXEXUTIVE SECRETARY JSSMVP SRI.B.S.BETKERUR, GUEST SPEAKER PROF.P.CHANDRASHEKARA DR.K.A.SUDHARSHANAMURTHY-HEAD DEPT MEDICINE, VICE PRINICIPAL JSSMC DR.M.D.RAVI (L–R)


















FELICITATIONS TO Prof.Dr P.CHANDRASEKHARA HOD of Medicine

MVJ Medical College Ex Nodal officer, ART unit, B&LC Hospital by EXEXUTIVE SECRETARY JSSMVP SRI.B.S.BETKERUR

KNOW YOUR HISTORY




















The Caduceus – which adorns the banners, logo of all the medical institutions, finds place on the vehicles of doctors. What does it really symbolize?

An insignia used by the medical profession; modeled after the staff of Hermes; (Greek mythology) messenger and herald of the gods; god of commerce and cunning and invention and theft; is identified with Roman god Mercury.

The wings represent transcendence, diligence, and activity. The wand represents power. The axis mundi, down which messages travel between heaven and earth. The double serpents represent the dualist opposites, healing versus poison, illness versus health. They also represent mediation between the upper and lower realms- Good and Evil. Altogether the perfect symbol of office for the medical manager, interlocutor, and healer.

AN AIRY IMAGE























K.A.Sudharshana Murthy, Kiran.H.S, Balaji.K

A 30 year old man presented with headache, vomiting, altered sensorium and seizures. On examination, he was comatose with meningeal signs. Cranial CT scan demonstrated Pneumocephalus. He died shortly afterwards.


CT Report:
Moderate dilatation of lateral ventricles with intraventricular air pockets; small intracranial air pockets in the sulci, bilaterally; CT features are suggestive of (?) meningitis with ventriculitis.

Pneumocephalus is “the presence of air or gas within the cranial cavity.”It can be classified as extradural, subdural, subarachnoid, intracerebral, and intraventricular. Pneumocephalus is usually caused by trauma or surgery. Spontaneous, non-traumatic pneumocephalus is an uncommon condition. In the absence of head trauma, meningitis is an extremely rare cause of pneumocephalus & should raise the suspicion of anaerobic infection. It may be due to anaerobic or aerobic or mixed infection also. The majority of patients do not survive.
Acknowledgement:
Our sincere thanks to Dr.Nagaraj Murthy,Asso.Prof of Radiology)

REFERENCES

1. Jayaram S, Jadhav S, Rathod D, Tarvade S, Sornan A.Meningitis: an unusual cause of pneumocephalus.J Assoc Physicians India 2004;52:67-8
2. Parmar MS. Pneumocephalus associated with Bacteroides fragilis meningitis. J Postgrad Med 2004;50:272-3.
3. Tanaka T, Takagi D, Takeyama N, Kitazawa Y. “Spontaneous” pneumocephalus associated with aerobic bacteremia. Clin Imaging 1989;13:134 -9.

Saturday, January 23, 2010

World Epilepsy Celebrations

















INAGURAL FUNCTION OF WORLD EPILEPSY DAY BY DR.BASAVANA GOWDAPPA PRINCIPAL JSSMC DR.S.HARSHA, DR.B.S.KESHAVA, DR.KVEERABHADRAPPA, DR.K.A.SUDHARSHANA MURTHY


World Epilepsy Day was celebrated by the Department of Neurology JSS Hospital on 17th November 2009 in a novel way by conducting a "Patient Awareness/ Education Program”. The idea was to provide comprehensive information about epilepsy to the patients, their family members and caregivers, also address all issues concerning this disease and try to resolve their doubts by interaction.

The program was held at Sri. Rajendra Auditorium, JSS Hospital, Mysore on17th November 2009. The programme was inaugurated by Dr. H. Basavanagowdappa,Professor of Medicine & Principal, JSS Medical College, Mysore. Delivering the key-note address he stressed the
importance of educating the patient and public in order to eradicate the social stigma attached to epilepsy. Dr.K.A.Sudharshana Murthy, Professor and Head Medicine spoke on the need to emphasize the importance of regular medications and compliance so that the patient can be completely seizure free. Dr.K.Veerabhadrappa Medical Superintendent of JSS Hospital spoke on the role played by the family members and care givers in empowering the patient. Patient education lectures by Dr.Harsha,S, Dr.B.S.Keshava, Neurologists JSSMC&Hospital, detailed the clinical features, causes of epilepsy and the available treatment modalities, duration of treatment and advances in the treatment. Dr.Ambareesh Bandiwada, Professor,OBG addressed the problems faced by an epileptic lady during pregnancy and the advised on precautions to be followed by women of child bearing age withepilepsy.Dr.Narayanappa Professor and HOD of peadiatrics spoke on issue of children with seizures. Dr.T.S.S.Rao Prof and HOD of Psychiatry dealt behavioral problems in epilepsy and the role his family plays in this aspect. These lectures were followed by a very lively inter-active session with the audience. Later there was a very good video presentation on epilepsy, management issues and advice.

WORLD DIABETES DAY

World Diabetes Day 2009 was commemorated by the Department of Medicine, JSS Medical College & Hospital by conducting a Diabetes Detection Camp for the inmates of Central Prison, Mysore in the prison campus on 14th November. The camp was inaugurated by His Holiness Jagadguru Sri Sri Shivarathri Deshikendra Mahaswamiji and Siddaganga Mutt junior pontiff Niranjana Pranava Swaroopi Sri Sri Siddalinga Swamiji in the presence of Prison Superintendent Mr.K.Veerabhadraswamy. Dr.K.A.Sudharshana Murthy, H.O.D. Medicine gave a brief introduction to the importance of World Diabetes Day. Dr.H.Basavana Gowdappa, Principal, JSSMC, stressed on importance of detecting Diabetes at an early stage. His Holiness Jagadguru Sri Sri Shivarathri Deshikendra Mahaswamiji advised inmates not to neglect their health and, to be good and responsible citizens and be a role model for others after their release. Sri Sri Siddalinga Swamiji lauded the efforts of holding a health camp for jail inmates and emphasized the importance of social justice and equanimity of health care.The team of doctors which included Dr.Mahesh.M, Dr.SureshBabu.M, Dr.N.Vijay Cheluvaraj, Dr.Suchismitha, Dr.Syed Hidayathulla, Dr.Jeevan.H.R, Dr.Tejamani.C.M, and Dr.Shashidhara.M conducted screening of Diabetes and Hypertension for prison inmates under the guidance of Dr.K.A.Sudarshana Murthy. A detailed clinical examination was conducted and blood sugar and ECG were done. Mr.Mahadev and Mr.Gurumallesh ECG technicians assisted the team. Screening revealed 13 new diabetics and 8 Hypertensives of the 100 inmates. They were initiated on treatment and were advised on further evaluation and follow-up. The programme was supported by Mr. Ajay and Mr. Manjunath from Ranbaxy Pharmaceuticals.






WORLD DIABETES DAY CELEBRATION ON NOVEMBER 14th 2009 AT MYSORE CENTRAL JAIL IN THE DIVINE PRESENCE OF .HIS HOLINESS SRI SRI SIVARATRI DESIKENDRA SWAMIJI & NIRANJANA PRANAVASWAROOPI SRISRI SIDDALINGA SWAMIJI SIDDAGANAGA MUTT

H1N1 Influenza (Swine Flu)

Dr. Mahesh P A
Associate Professor, Dept Pulmonology, JSS Medical College, Mysore


Introduction:
•In April 2009, the World Health Organization (WHO) received reports of sustained person to person infections with a novel influenza A (H1N1) virus in Mexico and the United States.
•Subsequent international spread led WHO to declare on 11 June 2009that the first influenza pandemic in 41 years had occurred.
•This 2009 pandemic H1N1 influenza virus has now spread worldwide, with confirmed cases of pandemic H1N1 virus infection reported in more than 100 countries in all 6 WHO regions.

Earlier major Influenza Pandemics:
•1918: The Spanish flu pandemic remains the most devastating outbreak of modern times. Caused by a form of the H1N1 strain of flu, it is estimated that up to 40% of the world's population were infected, and more than 50 million people died, with young adults particularly badly affected
•1957: Asian flu killed two million people. Caused by a human form of the virus, H2N2, combining with a mutated strain found in wild ducks. The impact of the pandemic was minimized by rapid action by health authorities, who identified the virus, and made vaccine available speedily. The elderly were particularly vulnerable
•1968: An outbreak first detected in Hong Kong, and caused by a strain known as H3N2, killed up to one million people globally, with those over 65 most likely to die

H1N1 Virus
The present Influenza virus developed from a mixing of genetic material of swine, avian and human influenza virus. The mixing of the different influenza strains occurred in the pigs. When there is a gross change in the genetic composition of the virus it is called as ‘antigenic shift’. Once the virus was transmitted to humans, subsequent transmission has occurred from human to human and has resulted in the present pandemic. There has been a resurgence in the number of cases and deaths due to H1N1 with 1000 patients dying of the disease in one week alone.

In an interesting study on how this pandemic virus interacts with other flu viruses, three different flu viruses were competed against the H1N1 inside ferrets
The study demonstrated that H1N1 is clearly superior to other influenza viruses.
–Replicates twice as fast as other viruses
–Spreads deeper into the lungs whereas other viruses were still in the nasal passages
–More communicable
–Did not show any signs of mixing with other strains to create a super bug


Clinical Presentation of Swine Flu:

The clinical presentation of Swine flu can vary between being asymptomatic to a florid pneumonia with ARDS and multi organ failure. The clinical diagnosis of Swine flu is suspected by epidemiological data and confirmed by laboratory methods. However, the initial treatment should not be withheld pending laboratory reports. Uncomplicated Swine flu presents with fever, cough, sore throat, rhinorrhea, myalgia, malaise. No breathlessness, cyanosis or severe dehydration is observed. Gastrointestinal symptoms like diarrhea and vomiting may be present, especially in children. In complicated cases, dyspnea, tachypnea, hypoxia, radiological pneumonia, severe dehydration is commonly observed. Different target organ involvement including encephalopathy, renal failure, hepatic failure, septic shock, rhabdomyolysis and myocarditis are common. It is also observed that associated co-morbidities like asthma, COPD, diabetes, cardiovascular, hepatic or renal diseases also worsen in these patients with swine flu. Progression from an uncomplicated case to a complicated case can sometimes occur rapidly. An initial period of rhinorrhea and fever progresses to tachypnea, dyspnea, cyanosis, hemoptysis, shock, altered consciousness, drowsy, convulsions, confusion, weakness or even paralysis within a short period and therefore careful observation on stable patients is important until they fully recover. Evidence of sustained viral replication or a complicating bacterial infection is suspected if the fever persists beyond 3 days. In subjects with severe dehydration, decreased activity, lethargy, dizziness and decreased urine Decreased activity, lethargy, dizziness and decreased urine output are usually observed.


Recommendations for treatment from the Government of India

•Category A
–Patients with mild fever plus cough / sore throat with or without body ache, headache, diarrhoea and vomiting
–Do not require oseltamivir
–Monitored for progress and reassessed at 24-48 hours
–No testing for H1N1
–Avoid going out and mixing with people

•Category B (i)
–In addition to all the signs and symptoms mentioned under Category-A, if the patient has high grade fever and severe sore throat
–May require home isolation
–Treat with Oseltamivir


•Category B (ii)
–In addition to all the signs and symptoms mentioned under Category-A, individuals having one or more of the following high risk conditions
–Children less than 5 years old;
–Pregnant women;
–Persons aged 65 years or older;
–Patients with lung diseases, heart disease, liver disease, kidney disease, blood disorders, diabetes, neurological disorders, cancer and HIV/AIDS; Patients on long term cortisone therapy
–Treat with Oseltamivir

•Category C
–Symptoms of category A and/or B
–Breathlessness, chest pain, drowsiness, fall in blood pressure, sputum mixed with blood, bluish discoloration of nails
–Irritability among small children, refusal to accept feed
–Worsening of underlying chronic conditions
–Immediate hospitalization, testing for H1N1 and treatment


Current antiviral susceptibility according to WHO












Key principles guiding selection of antivirals during the H1N1 pandemic

•An antiviral should not be used if it known that the strain is likely to be resistant
•When more than one virus is circulating, more than one antiviral may be used to increase the probability of providing coverage with at least one effective agent
•There should be continual monitoring for drug resistance in the local population

Drugs for treatment
Oseltamivir – 75 mg twice daily
Zanamivir – 10 mg twice daily



Chemoprophylaxis
High risk settings as in Nursing home residents, close contact with a case of swine flu
High gain settings as medical and paramedical personnel taking care of patients with swine flu.

Drugs for Chemoprophylaxis
Oseltamivir – 75 mg once daily
Zanamivir – 10 mg once daily

The following Personal Protection Equipments need to be used by health care workers taking care of patients with H1N1 where there is a risk of aerosol generation as in nebulisation, ventilation and endotracheal suction
Mask - N95 respirator
Gowns
Gloves
Eye protection and face shield
Health care workers not involved in aerosol generation can use a triple layer surgical mask. However, care needs to be taken that the mask should not be reused or used when wet.

One of the most important tools for prevention of infections for health care workers and general population is frequent hand washing.

An interesting presentation Carcinoma of Unknown Primary (CUP)

K.A.Sudharshanamurthy, K.M.Srinath, M.G.Mahesh, R.Sunil
Medicine 2 Unit JSSMC & Hospital Mysore

A 65 year old male patient, an agriculturist presented with chief complaints of Fever and generalized weakness of 1 month duration .He was a chronic smoker with no significant past history or family history. General physical examination and systemic examination were normal with no detectable clinical findings. Investigations were carried to evaluate cause of fever and all the investigations for the fever work up were normal except for chest radiograph which was suggestive of miliary mottling. HRCT Thorax was reported to be having features of ILD. During the course in the hospital, patient continued to have fever and developed mild cognitive dysfunction. Neurological examination revealed only an extensor plantar reflex on the left side with no motor deficits. CT Scan Head revealed a small, irregular, enhancing hyperdense lesion involving parietal cortex suggestive of neoplastic lesion. MRI Brain with GADO and MRS revealed features suggestive of primary neoplastic lesion- Glioma.



























Patient was subjected to craniotomy and excision of the tumor. Patient developed severe hyponatremia in the postoperative period, which was successfully treated. Histopathology of the tumour revealed metastatic adenocarcinoma with a probable primary in the lung. Patient and his family were not willing for further evaluation.



















Cancer of unknown primary site (CUP) is a common clinical entity, accounting for 2 percent of all cancer diagnoses in the Surveillance, Epidemiology and End Results (SEER) registries between 1973 and 1987. The designation Carcinoma of Unknown Primary site implies that the pathologist, although confident of the diagnosis of malignancy, is unable on light microscopy to distinguish between a carcinoma, sarcoma or a hematologic neoplasm. The use of immunohistochemistry, electron microscopy, and chromosomal analysis has given a scope of identifying most of the neoplasms of unknown primary site as carcinomas, sarcomas, or lymphomas. The decisions confronting the clinicians are multifold: firstly, which investigations are justified to determine the primary site and to what extent should patients be examined? Which therapeutic regimen have to be adapted and worse, the prognostication.

Cancers of unknown primary are categorized into four major subtypes by routine light microscopy criteria:
1. Adenocarcinoma well–moderately differentiated – 50%
2. Undifferentiated or poorly differentiated adenocarcinomas - 30%
3. Squamous cell carcinomas – 15% and
4. Undifferentiated neoplasms - 5%.

Early dissemination, clinical absence of primary tumor, unpredictability of metastatic pattern and aggressiveness constitute the fundamental characteristics of these tumors. Early dissemination is reflected in the clinical absence of symptoms related to a primary tumor. More than 50% of CUP patients present with multiple sites of involvement, while the rest have a single site, most commonly in liver, bone, lung or lymph nodes.



















The initial work-up of patients presenting with a presumed CUP should not be exhaustive, and should instead be geared toward evaluation of likely primary sites. This initial evaluation should include, a thorough history and physical examination (including a pelvic examination in women and a prostate examination in men), complete blood count, urinalysis, blood chemistries, a chest radiograph, and computed tomography (CT) of the abdomen and pelvis. The use of immunohistochemistry, electron microscopy, and chromosomal analysis may permit the identification of most neoplasms of unknown primary site as carcinomas, sarcomas, or lymphomas.


Immunoperoxidase Markers Useful in CUP
Tumour Type Immunoperoxidase Marker
Carcinoma Cytokeratin, EMA
Lymphoma CLA,EMA
Sarcoma Vimentin, Desmin, Factor VIII Ag
Melanoma S-100,HMB-45,Vimentin-45,NSE
Neuro Endocrine Chromogranin,Synaptophysin,Cytokeratin,EMA,NSE
Germ Cell Cytokeratin,EMA,HCG,AFP
Prostate Cancer PSA, Cytokeratin,EMA
Thyroid Cancer Thyroglobulin,Cytokeratin, EMA,Calcitonin
Breast Cancer Cytokeratin,EMA,PR,ER
AFP-Alpha Feto Protein, CLA-Common Leucocyte Antigen, EMA-Epithelial
Membrane Antigen, ER-Estrogen Receptor, HCG-Human Chorionic Gonadotropin,
NSE-Neuron specific enolase, PSA-Prostate Specific Antigen, PR-Progesterone
Receptor

Prognostic Factors
Patients with CUP have a limited life expectancy with a median survival of ∼6–9 months. However, some subsets have a better prognosis and enjoy longer survival.
Retrospective analyses have identified clinical and pathologic features associated with a favorable response to treatment with empiric chemotherapy. These include:
• Tumor location in lymph nodes or soft tissue in comparison, patients with involvement of the liver or bones have relatively poor prognosis.
• Fewer sites of metastatic disease
• Female sex
• Poorly differentiated carcinoma histology
• Good performance status
• Normal serum lactate dehydrogenase (LDH) level
• Normal serum albumin
• Normal lymphocyte count
Recommendations for the treatment of patients with CUP are
• All patients with good performance status should be considered for a trial of empiric chemotherapy.
• The best regimen has not been defined in prospective randomized trials. At present, the combination of Paclitaxel and Carboplatin is a reasonable choice for first-line therapy.
• The value of adding a third agent (either etoposide or gemcitabine) is unclear, based upon data from existing phase II trials.
• Patients with poor performance status are much less likely to benefit from chemotherapy, and optimal management may include supportive measures only.
















References:
1. Management of carcinoma of unknown primary site (CUP), any changes? Editorial Annals of Oncologv 12, 431-432. 2001
2. Cancer of unknown primary: biological and clinical characteristics
N. Pavlidis. Annals of Oncology 14 (Supplement 3): iii11–iii18, 2003
3. Muir C. Cancer of unknown primary site. Cancer 1995; 75: 353–356
4. Carcinoma of unknown primary site: treatment with 1-hour paclitaxel, carboplatin, and extended-schedule etoposide. Hainsworth JD; Erland JB; Kalman LA; Schreeder MT; Greco FA J Clin Oncol 1997 Jun;15(6):2385-93

Departmental Activities

Dr.K.A.Sudharshana Murthy, Prof & HOD of Medicine attended master class programme on 11.9.2009 at London conducted by BMJ.

Dr. K.A.Sudhrarshana Murthy, Prof & HOD of Medicine Chaired a session at state conference of Indian Association of Pathologist & Microbiologist on the topic ‘Interpretation of Liver Biopsy’ by Dr.Siddhartha Dutta Gupta, Prof. of pathology AIIMS, New Delhi.

Dr.M.Mahesh, Asso. Prof. of Medicine Conducted API – MPMRT UG QUIZ 2009 on 21-11-2009

Dr.Srinath.K.M. Asso. Prof. of Medicine presented a faculty lecture on “diabetic foot management” for department of medicine JSSMC on 28-10-2009

Dr.Srinath.K.M. Asso. Prof. of Medicine delivered a guest lecture on “Obesity & Pharmacological management” for IMA physicians & family physician of Madikeri Chapter on 21-11-2009.

Dr. Kiran.H.S, Asst. Prof. of Medicine delivered a faculty lecture: “HYPONATREMIA REVISITED & SIADH” on 28.10.2009 for dept of Medicine JSSMC.

Dr.Suresh Babu, Asso. Prof. of Medicine delivered a lecture on H1N1 Flu at JSS High School on the occasion of Jayanthi Celebration in the month of September.

Dr.M.Bhanu Kumar Asso. Prof. of Medicine delivered a guest lecture on Cardiac Rehabilitation Programme, in STEMI, organized by CSI, Mysore Chapter, on 26-12-2009.

Winners



Dr.SAJID SYED, PG IN GENERAL MEDICINE,
Won the 1st Prize in Short Topic discussion in the recently held MERT at Bangalore from 2nd – 8th October 2009















Dr.ASHIK SASIDHARAN, PG IN GENERAL MEDICINE,
Won the 1st Prize in Problem Case Discussion in the recently held MERT at Bangalore from 2nd – 8th October 2009