Q: Which one of the following is the risk for Linezolid associated lactic acidosis?

A) Diabetes
B) Decrease GFR (golmerular filtration rate)
C) Previously documented bacteremia
D) Age
E) Duration of therapy



Answer: E

One recent study of 72 patients, published in International Journal of Infectious Disease showed that a longer duration of linezolid use, i.e more than 6 weeks use is one of the risk factors for metabolic acidosis. There was no statistically significant difference according to age, estimated glomerular filtration rate, or diabetes. 




Reference:

 Im JH, Baek JH, Kwon HY, Lee JS. - Incidence and risk factors of linezolid-induced lactic acidosis - J Infect Dis. 2015 Feb;31:47-52.

Q: Out of following, which one has shown to decrease vasospasm after sub-arachnoid hemorrhage SAH)?

A) Hydralazine
B) Beta blocker
C) Clonidine
D) Statin
E) Vitamin B6


Answer: D

Guidelines from the American Stroke Society recommends to administer statin therapy to patients after SAH to prevent vasospasm, after few trials showed that statin treatment is beneficial for preventing vasospasm and improving outcome after SAH. The mechanism is uncertain. Recommended dose is either pravastatin 40 mg daily or simvastatin 80 mg daily within 48 hours of diagnosis of aneurysmal SAH.




References: 

1. Connolly ES Jr, Rabinstein AA, Carhuapoma JR, et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/american Stroke Association. Stroke 2012; 43:1711.

2. McGirt MJ, Lynch JR, Parra A, et al. Simvastatin increases endothelial nitric oxide synthase and ameliorates cerebral vasospasm resulting from subarachnoid hemorrhage. Stroke 2002; 33:2950.

3. Lynch JR, Wang H, McGirt MJ, et al. Simvastatin reduces vasospasm after aneurysmal subarachnoid hemorrhage: results of a pilot randomized clinical trial. Stroke 2005; 36:2024.

4. Sillberg VA, Wells GA, Perry JJ. Do statins improve outcomes and reduce the incidence of vasospasm after aneurysmal subarachnoid hemorrhage: a meta-analysis. Stroke 2008; 39:2622.

5. Liu Z, Liu L, Zhang Z, et al. Cholesterol-reducing agents for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev 2013; 4:CD008184.

Q: What is the best prevention of avoiding limb ischemia in insertion of Intra-Aortic Balloon Pump (IABP)?


Answer:  To avoid needle puncture which is too low.

If arterial needle puncture is too low in femoral area, probability is high of IABP insertion in one of the branches of femoral artery like superficial or profunda femoral artery. These branches are usually not large enough and may cause limb ischemia. 

ON HEMODIALYSIS-INDUCED HYPOTENSION

One common misconception on hypotension during hemodialysis is naive thinking that induction of intravascular volume depletion by rapid ultrafiltration causes the problem. But in actuality it is not the only mechanism as patients can tolerate same rate of fluid removal with pure hemofiltration.

 During conventional hemodialysis, the rapid diffusive removal of urea results in a reduction of the plasma osmolality. This creates two processes simultaneously. Firstly, water moves osmotically into the cells. Secondly, the rapid fall in plasma osmolality causes hemodynamic instability by interfering with sympathetic responsiveness to volume depletion.

Reference:

Bergstrom J, Asaba H, Furst P, Oules R. Dialysis, ultrafiltration, and blood pressure. Proc Eur Dial Transplant Assoc 1976; 13:293.

Post-intensive care syndrome (PICS)

Post-intensive care syndrome (PICS) is an extremely under recognised entity due to reasons as they usually happen outside of walls of ICU. It is defined as as new or worsening symptoms in three categories after a critical illness.

•  cognitive, or/and
•  psychiatric, or/and 
•  physical function 

Upto 50% of ICU discharged patients may suffer from some degree of PICS. Level of sickness is the biggest indicator particularly delirium, sepsis, ARDS, use of mechanical ventilation etc. It requires proper follow up and diagnostic evaluation. It may persist up to years and has been found to be associated with social and financial morbidities as well as increased risk of death.

Prevention is the best treatment by sedation and neuro-muscular blockade (if use) holidays and most importantly by early physical mobilization in ICU.

Another associated entity is  PICS-F (Post-intensive care syndrome -Family) in loved ones with sleep deprivation, depression, and PTSD. The best strategy to help out is the open and detailed communication.

References:

1. Needham DM, Davidson J, Cohen H, et al. Improving long-term outcomes after discharge from intensive care unit: report from a stakeholders' conference. Crit Care Med 2012; 40:502 

2.  Needham DM, Dinglas VD, Morris PE, et al. Physical and cognitive performance of patients with acute lung injury 1 year after initial trophic versus full enteral feeding. EDEN trial follow-up. Am J Respir Crit Care Med 2013; 188:567.  

3.. Jackson JC, Pandharipande PP, Girard TD, et al. Depression, post-traumatic stress disorder, and functional disability in the BRAIN-ICU study: a longitudinal cohort study. Lancet Respir Med 2014; 5:369. 

4. Hermans G, Van Mechelen H, Clerckx B, et al. Acute outcomes and 1-year mortality of intensive care unit-acquired weakness. A cohort study and propensity-matched analysis. Am J Respir Crit Care Med 2014; 190:410.

Q: All of the following may decrease the rate of Ventilator Associated Pneumonia (VAP) except? 

A) Oral hygiene via chlorhexidine mouthwash or gel
B) Head of bed elevation to reduce subglottic drainage
C)  Maintaining an ETT airway cuff pressure to 10 to 20 cm H2O. 
D) Minimizing transport out of the ICU 
E) Application of 5 to 8 cm H2O of PEEP



Answer:  C

All of the above have shown to decrease the rate of VAP, but cuff pressure of ETT should be maintained at 20 to 30 cm H2O. 

In above question choice D is an interesting choice, but rationale behind relationship of VAP and Minimizing transport out of the ICU is the observational studies showing bedside resuscitation bags as a source of bacterial contamination.


References:

1. Kollef MH, Von Harz B, Prentice D, et al. Patient transport from intensive care increases the risk of developing ventilator-associated pneumonia. Chest 1997; 112:765. 

2. Thompson AC, Wilder BJ, Powner DJ. Bedside resuscitation bags: a source of bacterial contamination. Infect Control 1985; 6:231. 

3. Weber DJ, Wilson MB, Rutala WA, Thomann CA. Manual ventilation bags as a source for bacterial colonization of intubated patients. Am Rev Respir Dis 1990; 142:892.

Q: 54 year old female is admitted to ICU with clonidine overdose. Patient appears very sedated. You are trying to avoid intubation. Which of the following drug may be use to reverse clonidine effect and may prevent intubation?

A) Flumazinil
B) Naloxone
C) Dexmedetomidine
D) Lopressor
E) Hemo-dialysis (HD)


Answer: B

Clonidine toxicity can be reversed with 1 to 2 mg x 1 dose of Naloxone, particularly in patients with CNS and respiratory depression. Interestingly, majority of patients who respond to naloxone do not require additional doses. If patient do not respond to x 1 attempt to Naloxone, further administration of Naloxone should be avoided and supportive care should be instituted till patient stabilized. And, if patient respond to Naloxone but symptoms recur later, intermittent doses can be used upto maximum of 10 mg. Continuous infusion should be preferably be avoided.

Flumazinil has no role in this situation
Dexmedetomidine and Lopressor may make symptoms worse, and
HD does not remove clonidine

Reference: 

1. Wiley JF 2nd, Wiley CC, Torrey SB, Henretig FM. Clonidine poisoning in young children. J Pediatr 1990; 116:654.

2. Spiller HA, Klein-Schwartz W, Colvin JM, et al. Toxic clonidine ingestion in children. J Pediatr 2005; 146:263.

Q: It is common for a patient to receive long term opiate infusion in ICU particularly while on ventilator. Abrupt discontinuation may lead to withdrawal symptoms. What various strategies may be used to prevent opiate withdrawal?


Answer;  Patient who requires more than few days of opiate infusion may subject to withdrawal symptoms which may include agitation, lacrimation, diaphoresis, mydriasis, diarrhea, tremor, tachycardia, hypertension etc. Few strategies which may be used

• Addition of clonidine
• Addition of dexmedetomidine
• conversion to oral opiates 
• de-escalating the dose instead of abrupt withdrawal, 
• Assurance 

References:

1. Honey BL, Benefield RJ, Miller JL, - Johnson PN. Alpha2-receptor agonists for treatment and prevention of iatrogenic opioid abstinence syndrome in critically ill patients. Ann Pharmacother 2009; 43:1506. 

2. Al-Qadheeb NS, Roberts RJ, Griffin R, et al. Impact of enteral methadone on the ability to wean off continuously infused opioids in critically ill, mechanically ventilated adults: a case-control study. Ann Pharmacother 2012; 46:1160. 

3. Maccioli GA. Dexmedetomidine to facilitate drug withdrawal. Anesthesiology 2003; 98:575.

Q: What is the 'rule of thumb' for titrating the neuro-muscular blockade (NMB) infusion in ICU?  

Answer: The depth of neuromuscular blockade should be monitored by peripheral nerve stimulation (PNS), popularly know as 'Train of Four' (TOF). In first 24 hours, it should be assessed every 2 hours and once goal of '2/4 TOF' is achieved, frequency can be decreased to q12 hours. 

As a 'rule of thumb' dose should be reduced approximately 10 percent if TOF is 0/4 or 1/4 - or increased by by 10 percent if TOF level is 3/4 or 4/4. 

Alike concept of 'sedation holiday' daily discontinuation of NMB should be performed to assess clinical progress and decrease complications, particularly critical illness myopathy.



Reference:

Murray MJ, Cowen J, DeBlock H, et al. Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient. Crit Care Med 2002; 30:142.

Q: Which of the following Neuro-muscular blockade should be avoided in cocaine overdose?

A) cisatracurium
B) succinylcholine
C) vecuronium
D) pancuronium
E) atracurium


Answer: B

Succinylcholine can prolong the effects of cocaine and is usually advised not be used in Rapid sequence intubation, if required. Rocuronium is preferred. It is not a absolute but a relative contraindication.

HAS-BLED score

Q: What is HAS-BLED score?


Answer:  The HAS-BLED score was developed as a practical risk score to estimate the 1-year risk for major bleeding in patients on anticoagulation (mostly coumadin) with atrial fibrillation. Risk progressively goes up as score goes up like score of 2 has risk of 4.1% in one validation study and 1.88 bleeds per 100 patient-years in another validation study. Likewise, score of 4 has risk of 8.9% in one validation study and 8.70 bleeds per 100 patient-years in another validation study.

Oral lidocaine for intractable hiccups

Interesting report 


BACKGROUND: Persistent and intractable hiccups are a rather rare, but distressing gastrointestinal symptom found in palliative care patients. Although several recommendations for treatment are given, hiccups often persist. 

 CASE REPORTS: We describe a new pharmacological approach for successfully treating hiccups in four cancer patients. In the first patient, chronic and intractable hiccups lasted for more than 18 months, but disappeared immediately after swallowing a viscous 2 % lidocaine solution for treatment of mucositis. Based on this experience, we successfully treated three further patients suffering from singultus using a lidocaine-containing gel. To our knowledge, this is the first report about managing hiccups by oral application of a lidocaine solution.


Reference:

Neuhaus T1, Ko YD, Stier S. - Successful treatment of intractable hiccups by oral application of lidocaine - Support Care Cancer. 2012 Nov;20(11):3009-11.  Epub 2012 Jul 22.

Q: In hemolytic Anemia? (Choose one)

A) LDH goes up, Reticulocyte count goes up, Indirect bilirubin goes up
B)  LDH goes up, Reticulocyte count goes up, Direct bilirubin goes up
C)  LDH goes up, Reticulocyte count goes up, Serum haptoglobin goes up
D)  LDH goes down, Reticulocyte count goes up, Serum haptoglobin goes down
E)  LDH goes down, Reticulocyte count goes down, Serum haptoglobin goes up



Answer: A

Hemolytic Anemia is a common entity in ICU particularly if any device is cannulated to patient. Few simple tips to diagnose hemolytic anemia is 

•  Increased indirect bilirubin concentration 
• Splenomegaly 
• Increased serum lactate dehydrogenase (LDH) concentration 
• Reduced or absent level of serum haptoglobin 
• Increased reticulocyte percentage or absolute reticulocyte number

Q: 32 year old female admitted to ICU with seizure, preceded by severe headache. There is a strong suspicion of subarachnoid hemorrhage (SAH). Noncontrast CT of head is reported negative. Neurosurgeon requests you to perform lumbar puncture (LP) to confirm SAH. As you collect all four test tubes of CSF, you suspect some 'pinkish' tinge in fluid. What is your suspicion? 

 Answer: Xanthochromia 

Xanthochromia which is actually a pinkish or a yellowish tint signifies, hemoglobin degradation products in CSF, and is highly suggestive of SAH. The best way to confirm xanthochromia is by comparing a vial of CSF with a vial of plain water held side by side against a white background in bright light. It is important to perform this visual inspection quickly after LP to distinguish it from traumatic LP. The presence of xanthochromia in just performed LP indicates that blood has been in the CSF for at least two hours.

Reference:

Wijdicks EF, Kallmes DF, Manno EM, et al. Subarachnoid hemorrhage: neurointensive care and aneurysm repair. Mayo Clin Proc 2005; 80:550.

Q: 21 year old male presented to ER with palpitations, sweating and headache. He was found to be hypertensive in ER. Urine tox screen was negative. Patient BP was unresponsive to Cardene drip and is admitted to ICU. On history taking, patient informed you that his symptoms started while night out with friends, drinking lot of wine, imported beer and eating huge amount of smoked meat. Patient is taking anti-depressant at home. You suspect pheochromocytoma but patient informed you that he has been worked up in past and is ruled out for pheochromocytoma? 



Answer: 

Combination of a monoamine oxidase (MAO) inhibitor drugs and the ingestion of tyramine-containing foods may produce symptoms similar to pheochromocytoma.

Major MAO inhibitors include antidepressant drugs tranylcypromine, phenelzine, and isocarboxazid. Foods contain relatively high concentrations of tyramine fermented cheeses, imported beer, Chianti, champagne, some wines, soy sauce, avocados, bananas, and any fermented, smoked, or aged fish or meat. These food should be avoided by patients on these antidepressants. Tyramine, which is produced from the bacterial breakdown of tyrosine, is normally inactivated by MAO in the intestinal tract. This inactivation does not occur in the presence of an MAO inhibitor, leading to the absorption of tyramine, which increases the release of norepinephrine from nerve endings and epinephrine from the adrenal gland.

A note on Fospropofol

 Fospropofol is a water-soluble propofol prodrug. It has various advantage due to its water solubility like less pain at the site of IV infusion, so can be given via peripheral IV with more comfort. It carries less chance for hyperlipidemia, and subsequently less chance for bacteremia. Because of said advantage, it is a good choice for use in short-term sedation for patients undergoing procedures such as endoscopy. Fospropofol is metabolized by alkaline phosphatases to propofol, formaldehyde, and phosphate. 

Q: 42 year old male in ICU went into grand mal seizure. 2 mg of  IV lorazepam is administrated but did not bring any relief. Another dose of 2 mg of lorazepam is ordered and simultaneously phenytoin is ordered. Which one caution should be exercise very closely while treating this patient?


Answer: Phenytoin is incompatible with almost any of the benzodiazepines, and should not be administrated with same IV line, otherwise will precipitate. Another IV line should be established ASAP. Similarly is true for phenytoin and any fluid with glucose/dextrose. This does not apply to fosphenytoin infusion.

Q: Which of the following drug overdose may presents as non-cardiogenic pulmonary edema?

A) Phenytoin
B) Furosemide 
C) Salicylate
D) Propofol
E) Lorazepam


Answer: C

Salicylate-induced noncardiogenic pulmonary edema is usually seen as an acute on chronic salicylate poisoning. Elderly people are more prone to it. Salicylate-induced pulmonary edema is considered as an absolute indication for hemodialysis. 

Phenytoin toxicity does not produce pulmonary edema. Furosemide is usually the treatment of cardiogenic pulmonary edema. It should be use with caution in non-cardiogenic pulmonary edema. Propofol infusion syndrome may cause acute MI and subsequently cardiogenic pulmonary edema. Heroin and Methadone are known to produce non-cardiogenic pulmonary edema but Lorazepam is not.

Q: Is it necessary to document fat globules in blood drawn from a wedged PA catheter to confirm diagnosis of Fat Embolism Syndrome? (Yes or No)?


Answer: NO

It is not necessary to document fat globules in sputum, urine, or blood drawn from a wedged PA catheter to confirm the diagnosis of Fat Embolism Syndrome. 50 percent of patients with fracture may have fat globules in serum without any sign, symptom or diagnosis of Fat Embolism Syndrome. This misconception probably arises from the notion that debris need to be documented in amniotic fluid embolism in blood drawn from a wedged PA catheter, which in contrast is not necessary in fat embolism syndrome.

Q: In OR "Cell Saver" technique  (intraoperative autologous transfusion or intraoperative autotransfusion)  is frequently used. Why it is important to wash the blood before infusion back into patient?


Answer: Blood from patient needs to be 

• processed/collected in a sterile, filtered reservoir, 
• centrifuged, which separates and concentrates higher density RBCs 
• washed – with an isotonic solution, and
• reinfused

Salvaged blood should be washed. Unwashed salvaged blood has residual anticoagulant, dysfunctional platelets, thrombogenic substances, free hemoglobin levels, and fat emboli.

The FOUR Score

Q: What advantage The FOUR score has over Glascow Coma Scale (GCS)?

Answer:  Glascow Coma Scale (GCS) cannot be administered to patients with an endotracheal tube. The FOUR Score is to created as a clinical grading scale for the assessment of patients with impaired level of consciousness that can be used in patients with or without endotracheal intubation.

The "FOUR" is an acronym for "Full Outline of UnResponsiveness", and the FOUR Score assesses four domains of neurological function:

• eye responses, 
• motor responses, 
• brainstem reflexes, and 
• breathing pattern.

Q: 23 year old male presented to ER with shortness of breath. Patient history is significant with mediastinal mass and had radiation and chemotherapy 2 months ago. Following is the CXR. What is your probable diagnosis?

Answer: Radiation Pneumonitis

Radiation Pneumonitis occurs at dose beyond 4500 rads and is likely to happen if dose  >6000 R for duration of 5-6 weeks. Concurrent or later chemotherapy increases the risk. It starts with  exudative phase, progress to organizing phase and to fibrotic phase.  It usually occurs 6 weeks up to 6 months after treatment. One diagnostic clue is its confinement to radiation portal. A straight line effect, which confines of the radiation port, is virtually diagnostic of radiation-induced lung injury. Exclusion of other possible causes of the findings, such as infection, thromboembolic disease, drug-induced pneumonitis etc. should be sought before final diagnosis. Further workup may require CT scan, ECHO and biopsy.

Steroids have been suggested as a treatment but may not be very helpful.

Q: 32 year old male is admitted to ICU after he was brought to ER from beach after his SCUBA diving. Patient was found to be hallucinating, short of breath and just don't look too well. Patient recovered after getting 100% oxygen and IVF in ER, which was continued in ICU. Patient wants to sign AMA as he has flight from Miami to Seattle in next 4 hours. What would be your suggestion?


Answer: Avoid Air travel.

Complications of SCUBA  include hypothermia, trauma, decompression sickness, and nitrogen narcosis. Decompression sickness occurs when a diver returns to the surface and gas tensions in the tissue exceeds the ambient pressure, leading to the liberation of free gas from the tissues in the form of bubbles. It may cause various nonspecific systemic symptoms and may be life-threatening with pneumothorax or involvement of CNS. Patient should avoid air travel for 12 hours after uneventful SCUBA diving and 48 hours or may be more in case of symptomatic air travel.



References:

1. Freiberger JJ, Denoble PJ, Pieper CF, et al. The relative risk of decompression sickness during and after air travel following diving. Aviat Space Environ Med 2002; 73:980.

Q: At what level of FiO2 oxygen toxicity may occur? (select one)

A) more than 40% for more than four days
B)  more than 60% for more than four days
C)  more than 80% for more than two days
D) 100% beyond 24 hours 
E) There is no well-defined threshold FiO2 or duration for oxygen toxicity



Answer: E

Objective of above question is to enhance the awareness of supplemental oxygen in ICU. Conventionally 60% of FiO2 is used as threshold for oxygen toxicity. But this is a huge misconception. There is no well-defined threshold or duration of supplemental oxygen below which oxygen toxicity may or may not occur. Any level of or duration of  supplemental oxygen therapy may cause various effects like absorptive atelectasis, worsening of  hypercapnia in COPD patients, airway injury as well as parenchymal lung injury. Underlying lung disease, overall functional and nutritional status, and previous exposure to high risk lung medicines particularly bleomycin exposure may cause oxygen toxicity at any level and at any duration. PaO2 between 60 and 70 mmHg and pulse-ox oxygen saturation around 92% should be sufficient and beyond this add relatively little to the oxygen content of the blood. Most importantly, along with optimum FiO2, optimal PEEP should be provided in ventilated patients.

Q: In acute Pancreatitis which IVF is preferred?


Answer: Lactated Ringer's (LR)

Though evidence is weak but at least one small study of 40 patients showed that fluid resuscitation with lactated Ringer's in acute pancreatitis may be more beneficial. Patients who received lactated Ringer's had significantly lower mean C-reactive protein (CRP) levels compared with patients who received normal saline (52 versus 104 mg/dL) and also a significantly less systemic inflammatory response syndrome (SIRS) after 24 hours (84 versus 0 percent). 


Reference:

Wu BU, Hwang JQ, Gardner TH, et al. Lactated Ringer's solution reduces systemic inflammation compared with saline in patients with acute pancreatitis. Clin Gastroenterol Hepatol 2011; 9:710.

Picture Diagnosis

Answer: Hepatic portal venous gas is a rare X-ray finding in extended bowel necrosis and predicts a very high mortality in patients who presents with clinical signs c/w bowel ischemia.

Q: 34 year old male admitted to ICU with viral entero-gastritis overnight for IV hydration due to 'soft blood pressure'. On call resident ordered ultrasound of abdomen, which accidentally diagnosed Autosomal dominant polycystic kidney disease (ADPKD). Patient is at high risk for which other diseases?


Answer: ADPKD is characterized by cysts in the kidneys, which eventually lead to End Stage Renal Disease (ESRD) usually in fifth decade and usually is associated with cysts in other organs. Patients are at risk and should be educate and screened for 

• Cerebral aneurysms 
• Hepatic and pancreatic cysts 
• Valvular heart disease 
• Colon diverticulum 
• Abdominal wall and inguinal hernia 
• Seminal vesicle cysts 
• Cervicocephalic artery dissections, 
• Dolichoectasias 
• Central retinal vascular occlusions

A note on Urea Diuresis

Urea acts as an osmotic agent and causes polyuria. Causes of large amounts of urea that may produce urea diuresis is various and less appreciated in ICUs like.  

• Administration of high amounts of protein in enteral feed or parenteral nutrition, which eventually will catabolized to urea.
• Resolution from azotemia after AKI (Acute Kidney Injury)
• In Rhabdomyolysis or decub. ulcers where muscle protein catabolism results in the production of urea.
• In rare cases, urea at a dose of 30 g/day is used to treat SIADH  by increasing urinary solute excretion and enhance water excretion.

Q: In which conditions hydronephrosis may occur without urinary obstruction?

Answer:  

Conventional wisdom is that hydronephrosis occurs only with urinary obstruction but hydronephrosis may occur without urinary obstruction when patient is prone to a large diuresis, which may distend the intrarenal collecting system, like in congenital nephrogenic diabetes insipidus.

Q: 58 year old male admitted to ICU with acute Cholecystitis. CT scan of abdomen showed additional finding of infra-renal Abdominal Aortic Aneurysm with diameter of 5 cm. In asymptomatic patients, what is the usual cut-off point to consider surgical intervention in AAA? 

A) 4 cm

B) 4.5 cm

C) 5 cm

D) 5.5 cm

E)  6 cm

Answer: D

Though many factors effect the decision to consider surgical intervention in asymptomatic AAA like age, gender, rate of expansion and other associated co-morbidities but in general 2009 guidelines from the Society for Vascular Surgery recommends observation for asymptomatic AAA <5.5 cm in diameter. For female gender, a lower threshold of 5 cm is also recommended for elective repair of asymptomatic AAA as studies have shown higher rate of rupture in women compared with men for AAA of the same diameter.

Reference:

Chaikof EL, Brewster DC, Dalman RL, et al. SVS practice guidelines for the care of patients with an abdominal aortic aneurysm: executive summary. J Vasc Surg 2009; 50:880.