“In my patient with abdominal pain, what physical exam finding can help differentiate abdominal wall from intra-abdominal sources of pain?”

Most doctors have received the following page at some point in their career: “Patient having abdominal pain, please come assess.” Carnett’s sign (described by British surgeon J.B. Carnett in 1926) is a physical exam finding that helps differentiate abdominal wall from intra-abdominal sources of pain. Once the tender spot is located, the test is considered positive when the patient’s pain increases upon tensing of the abdominal wall muscles– such as by raising both legs with straight knees or lifting the head and shoulders from the bed. Conversely, if the pain decreases with this maneuver, an intra-abdominal source is more likely1,2.

A positive Carnett’s sign should broaden the differential of abdominal pain to include: hernias, irritation of intercostal nerve roots, rectus sheath hematomas, myofascial pain, anterior cutaneous nerve entrapment (latter discussed in another pearl). In the appropriate clinical setting,  local corticosteroids or anesthetic injections, or the application of hot or cold packs may be therapeutic2,3.


  1. Carnett JB. Intercostal neuralgia as a cause of abdominal pain and tenderness. J Surg Gynecol Obstet 1926; 42:625-632.
  2. Bundrick JB, Litin SC. Clinical pearls in general internal medicine.  Mayo Clin Proceedings 2011;86: 70–74. 
  3. Suleiman S , Johnston DE.  The abdominal wall: an overlooked source of pain. Am Fam Physician 2001; 64: 431-8.

Contributed by Brad Lander MD, Mass General Hospital, Boston, MA.

“In my patient with abdominal pain, what physical exam finding can help differentiate abdominal wall from intra-abdominal sources of pain?”

When should I pay attention to the minimum inhibitory concentration (MIC) of an antibiotic despite the lab reporting it to be in the “Susceptible” range?

For most clinicians, the choice of antibiotic is based on the laboratory reporting of “Susceptible” (vs “Resistant”), not the actual MIC value of the drug.  However, despite the fact that much of the data is retrospective and the association of MIC within a susceptible range and clinical outcome may not necessarily be causal, many experts recommend caution when “high” MICs within a susceptible range are observed, as found in the following situations:   

  1. Vancomycin MIC >1 ug/ml in Staphylococcal aureus (methicillin-sensitive or –resistant) infections which may be associated with clinical failure and, at times, increased mortality1,2.
  2. Ciprofloxacin or levofloxacin MIC>0.25 ug/ml in bacteremia caused by Gram-negative bacilli (including Enterobacteriacae as well as Pseudomonas aeruginosa) which may be associated with adverse outcome (eg, longer average hospital stay post-culture and duration of infection) but not necessarily mortality3-5.
  3. Levofloxacin MIC ≥ 1.0 ug/ml in Streptococcus pneumoniae infections, which may be associated with adverse clinical outcome based on drug pharmacodynamics and anecdotal reports of treatment failure6,7.


Contributed in part by Nick Van Hise, Pharm.D., BCPS, Infectious Diseases Clinical Pharmacist, Edward-Elmhurst Hospitals, Naperville, Illinois


  1. Jacob JT, DiazGranados CA. High vancomycin minimum inhibitory concentration and clinical outomces in adults with methicillin-resistant Staphylococcus aureus infections: a meta-analysis. Int J Infect Dis 2013;17:e93-e100.
  2. Kalil AC, Van Schooneveld TC, Fey PD, et al. Association between vancomycin minimum inhibitory concentration and mortality among patients with Staphylococcus aureus bloodstream infections: A systematic review and meta-analysis. JAMA 2014;312:1552-1564.
  3. DeFife R, Scheetz MH, Feinglass J, et al. Effect of differences in MIC values on clinical outcomes in patients with bloodstream infections caused by Gram-negative organisms treated with levofloxacin. Antimicrob Agents Chemother 2009;53:1074-79.
  4. Falagas ME, Tansarli GS, Rafailidis PI, et al. Impact of antibiotic MIC on infection outcome in patients with susceptible Gram-negative bacteria a systematic review and meta-analysis. Antimicrob Agents Chemother 2012;56:4214-22.
  5. Zelenitsky SA, Harding GKM, Sun S, et al. Treatment and outcome of Pseudomonas aeruginosa bacteremia: an antibiotic pharmacodynamics analysis. J Antimicrob Chemother 2003;52:668-674.
  6. Davidson R, Cavalcanti R, Brunton JL, et al. Resistance to levofloxacin and failure of treatment of pneumococcal pneumonia. N Engl J Med 2002;346:. 2002;346:747-50.
  7. De Cueto M, Rodriguez JM, Soriano MJ, et al. Fatal levofloxacin failure in treatment of a bacteremic patient infected with Streptococcus pneumoniae with a preexisting parC mutation. J Clin Microbiol 2008;46:1558-1560.
When should I pay attention to the minimum inhibitory concentration (MIC) of an antibiotic despite the lab reporting it to be in the “Susceptible” range?

What is the connection between cirrhosis and adrenal insufficiency (AI)?

The reported prevalence of AI in patients with liver disease varies widely (30-60%)1. However, there is no consensus on how to define AI in such patients, nor is the methodology for its evaluation standardized.  A common criticism is the frequent reliance on total, not free, serum cortisol in cirrhosis which may overestimate the prevalence of AI because cortisol is bound to corticosteroid binding globulin and albumin, commonly found at lower concentrations in cirrhosis. However, even when based on measuring free cortisol, AI is found in 12%-29% of clinically stable cirrhotic patients1.

 Secondary AI due to hypothalamic-pituitary dysfunction has been reported in Child-Pugh class A, B, and C patients (42%, 69%, and 80%, respectively)2. The mechanism of AI in cirrhosis is unclear, but low serum cholesterol in cirrhosis leading to lack of substrate for steroidogenesis, and increased levels of circulating endotoxin and pro-inflammatory cytokines impairing the hypothalamic-pituitary-adrenal axis have been postulated1.



  1. Fede G, Spadaro L, Purrello F. Review: adrenal insufficiency in liver disease. J Liver 2014;3:1.
  2. Zietz, B, Lock, G, Plach, B, et al. Dysfunction of the hypothalamic-pituitary-glandular axes and relation to Child-Pugh classification in male patients with alcoholic and virus-related cirrhosis. Eur J Gastroenterol Hepatology 2003;15:495-501.
What is the connection between cirrhosis and adrenal insufficiency (AI)?

What causes the “tree-in-bud” (TIB) opacities on the chest CT images of my patient with cough?

TIB opacities represent a normally invisible branches of the bronchiole tree (≤1 mm in diameter) that are severely impacted with mucous, pus, or fluid, with resultant dilatation and “budding” of the terminal bronchioles ( ≥2 mm in diameter)1 (photo).

Although initially described in 1993 as a thin-section chest CT finding in active tuberculosis, TIB opacities are by no means restricted to a specific lung entity, and may be of infectious as well as non-infectious causes.

TIB is most commonly seen with infectious bronchiolitis caused by bacteria (particularly Staphylococcus aureus, Hemophilus influenzae), mycobacteria (including atypical mycobacteria), viruses (eg, respiratory syncytial virus, cytomegalovirus), and fungi (eg, Pneumocystis jirovecii, Aspergillus sp.)1,2.

Non-infectious causes include inhalation of toxic gases, connective tissue disorders (eg, rheumatoid arthritis, Sjögren syndrome), cystic fibrosis, Kartagener syndrome, and non-infectious bronchiolitis (eg, obliterative bronchiolitis). Malignancy-related causes include chronic lymphocytic leukemia and pulmonary tumor embolism in breast, liver, kidney, stomach, prostate and ovarian cancers3.


  1. Collins J, Blankenbaker D, Stern EJ. Ct patterns of bronchiolar disease: What is “tree-in’bud”? AJR 1998;171:365-70.
  2. Rossi SE, Franquet T, Volpacchio M, et al. Tree-in-bud pattern a t thin-section CT of the lungs: radiologic-pathologic overview. RadioGraphics 2005;25:789-801.
  3. Terhalle E, Gunther G. “Tree-in-bud”: thinking beyond infectious causes. Respiration 2015;89:162-165.



Photo: TIB opacities in a 50 year old man with productive cough and shortness of breath caused by infectious bronchiolitis.



What causes the “tree-in-bud” (TIB) opacities on the chest CT images of my patient with cough?

How does cold weather induce angina pectoris (AP) in some patients with coronary artery disease?

Although it is well known that exposure to cold can provoke AP in some patients with coronary artery disease1, a unifying mechanism for its explanation has yet to be found.

One study involving subjects with exertional AP who inhaled cold air (-20 C°) during cardiac catheterization found no evidence of reactive constriction of large coronary arteries2, while another study involving patients with >50% coronary stenosis undergoing cold pressor test ( placing patient’s hand and forearm in ice water for 90 seconds), demonstrated a 39% decrease in coronary blood flow3.  

 Another experiment involving patients undergoing exercise treadmill testing at 6 and 25 C° found an increase in serum norepinephrine levels, increase in blood pressure and an increase in myocardial oxygen demand in all subjects on exposure to cold air3.  It concluded that compared to patients without cold-induced AP, patients with cold-induced AP may not have a reflex decrease in their heart rate, possibly due to a baroreceptor dysfunction. 


  1. Marchant B, Donaldson G, Mridha K. et al. Mechanisms of cold intolerance in patients with angina. J Am Coll Cardiol 1994;23:630-6.
  2. Hattenhauer M, Neill WA. The effect of cold air inhalation on angina pectoris and myocardial oxygen supply. Circulation 1975;51:1053-1058.
  3. Nabel EG, Ganz P, Gordon JB, et al. Dilation of normal and constriction of atherosclerotic coronary arteries caused by the cold pressor test. Circulation 1988;77:43-52.
How does cold weather induce angina pectoris (AP) in some patients with coronary artery disease?