My patient with angina symptoms also complains of neck pain with left arm numbness. Could they be related?

Short answer, yes! Anterior chest pain associated with cervical intervertebral disk disease, ossified posterior longitudinal ligament or other spinal disorders is sometimes referred to as “cervical angina” (CA) or “pseudoangina” and is an often overlooked source of non-cardiac chest pain. 1-5

Although its exact prevalence is unknown, 1.4% to 16% of patients undergoing cervical disk surgery may have symptoms of CA. 1 Conversely, 1 study reported 5% of patients with angina pectoris having cervical nerve root pathology.5 Many patients describe their chest pain as “pressure” or crushing in quality mimicking typical cardiac ischemia chest pain, often resulting in extensive cardiac workup.  To add to the confusion, some patients even respond to nitroglycerin! One-half of patients also experience autonomic symptoms such as dyspnea, vertigo, nausea, diaphoresis, pallor, fatigue, and diploplia.1

Certain clues in the patient’s presentation should help us seriously consider the possibility of CA: 1-3

  • History of cervical radiculopathy eg, subjective upper extremity weakness or sensory changes, occipital headache or neck pain
  • Pain induced by cervical range of motion or movement of upper extremity
  • History of cervical injury or recent manual labor (eg, lifting, pulling or pushing)
  • Pain lasting greater than 30 min or less than 5 seconds and not relieved by rest
  • Positive Spurling maneuver ie, reproduction of symptoms by rotating the cervical spine toward the symptomatic side while providing a downward compression through the patient’s head

CA is often attributed to cervical nerve root compression, likely mediated by compression of C4-C8 nerve roots which also supply the sensory and motor innervation of the anterior chest wall.

Bonus Pearl: Did you know that experimental stimulation of spinothalamic tract cells in the upper thoracic and lower cervical segments have been shown to reproduce angina pain? 6

References

  1. Susman WI, Makovitch SA, Merchant SHI, et al. Cervical angina: an overlooked source of noncardiac chest pain. The Neurohospitalist 2015;5:22-27. https://www.ncbi.nlm.nih.gov/pubmed/25553225
  2. Jacobs B. Cervical angina. NY State J Med 1990;90:8-11. https://www.ncbi.nlm.nih.gov/pubmed/2296405
  3. Sheps DS, Creed F, Clouse RE. Chest pain in patients with cardiac and noncardiac disease. Psychosomatic Medicine 66:861-67. https://www.ncbi.nlm.nih.gov/pubmed/15564350
  4. Wells P. Cervical angina. Am Fam Physician 1997;55:2262-4. https://www.ncbi.nlm.nih.gov/pubmed/9149653
  5. Nakajima H, Uchida K, Kobayashi S, et al. Cervical angina: a seemingly still neglected symptom of cervical spine disorder. Spinal Cord 2006;44:509-513. https://www.ncbi.nlm.nih.gov/pubmed/16331305
  6.  Cheshire WP. Spinal cord infarction mimicking angina pectoris. Mayo Clin Proc 2000;75:1197-99. https://www.ncbi.nlm.nih.gov/pubmed/11075751

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My patient with angina symptoms also complains of neck pain with left arm numbness. Could they be related?

How can I distinguish cardiac asthma from typical bronchial asthma?

Certain clinical features of cardiac asthma, defined as congestive heart failure (CHF) associated with wheezing, may be useful in distinguishing it from bronchial asthma, particularly in older patients with COPD (1-3).
• Paroxysmal nocturnal dyspnea associated with wheezing
• Presence of rales or crackles, ascites or other signs of CHF
• Poor response to bronchodilators and corticosteroids
• Formal pulmonary function test with bronchoprovocation demonstrating minimal methacholine response.

 
Cardiac asthma is not uncommon. In a prospective study of patients 65 yrs of age or older (mean age 82 yrs) presenting with dyspnea due to CHF, cardiac asthma was diagnosed in 35% of subjects. Even in non-elderly patients, cardiac asthma has been reported in 10-15% of patients with CHF (2).

 
The mechanism(s) underlying cardiac asthma is likely multifactorial. Pulmonary edema and pulmonary vascular congestion have traditionally been considered as key factors either through edema in the interstitial fluid of bronchi squeezing the bronchiolar lumen or by externally compressing the entire airway structure and the bronchiole wall. Reflex bronchoconstriction involving the vagus nerve, bronchial hyperreactivity, systemic inflammation, and airway remodeling may also play a role (1,3). 

 
Treatment of choice for cardiac asthma typically includes diuretics, nitrates and morphine, not bronchodilators or corticosteroids (1,3). 

 
Bonus Pearl: Did you know that the term “cardiac asthma” was first coined by the Scottish physician, James Hope, way back in 1832 to distinguish it from bronchial asthma!

 

References
1. Litzinger MHJ, Aluen JKN, Cereceres R, et al. Cardiac asthma: not your typical asthma. US Pharm. 2013;38:HS-12-HS-18. https://www.uspharmacist.com/article/cardiac-asthma-not-your-typical-asthma
2. Jorge S, Becquemin MH, Delerme S, et al. Cardiac asthma in elderly patients: incidence, clinical presentation and outcome. BMC Cardiovascular Disorders 2007;7:16. https://www.ncbi.nlm.nih.gov/pubmed/17498318
3. Tanabe T, Rozycki HJ, Kanoh S, et al. Cardiac asthma: new insights into an old disease. Expert Rev Respir Med 2012;6(6), 00-00. https://www.ncbi.nlm.nih.gov/pubmed/23234454

 

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How can I distinguish cardiac asthma from typical bronchial asthma?

Should I consider fosfomycin in the treatment of urinary tract infection in my male patient with suspected prostatitis?

Although fosfomycin (FM) has been approved by the FDA only for the treatment of uncomplicated urinary tract infection (UTI) in women, it may also have a role in the treatment of acute and chronic prostatitis among males given its favorable levels in the prostate tissue. 1-5

Despite lack of studies comparing the efficacy of FM with that of commonly used antibiotics for treatment of prostatitis, the potential utility of FM is supported by several reports of its efficacy in the treatment of prostatitis, including those caused by extended-spectrum beta-lactamase (ESBL)-producing gram-negative rods. 1,4-5

When considering FM for treatment of prostatitis, a higher dose than customary may be needed (3 g once daily, not every 48-72 h) . 4 Although the optimal duration of therapy with FM is unclear in this setting, 12-16 weeks of therapy was used in 2 patients with recurrent UTIs and prostatitis due to multi-drug resistant ESBL-positive E. coli. 4

Given its pharmacokinetics and lack of proven efficacy, avoid FM in pyelonephritis, perinephric abscess or UTI with bacteremia. 2

References

  1. Falagas ME, Vouloumanou EK, Samonis G, et al. Fosfomycin. Clin Microbiol Rev 2016;29:321-347. https://www.ncbi.nlm.nih.gov/pubmed/26960938
  2. Wankum M, Koutsari C, Gens K. Fosfomycin use. Pharmacy Times. November 30, 2017. https://www.pharmacytimes.com/publications/health-system-edition/2017/november2017/fosfomycin-use
  3. Cunha BA, Gran A, Raza M. Persistent extended-spectrum β-lactamase-positive Escherechia coli chronic prostatitis successfully treated with a combination of fosfomycin and doxycycline. International J Antimicrob Agents 2015;45:427-29. https://www.ncbi.nlm.nih.gov/pubmed/25662814
  4. Grayson ML, Macesic N, Trevillyan J, et al. Fosfomycin for treatment of prostatitis: new tricks for old dogs. Clin Infect Dis 2015;61:1141-3. https://www.ncbi.nlm.nih.gov/pubmed/26063723
  5. Falagas ME, Rafailidis PI. Fosfomycin: the current status of the drug. Clin Infect Dis 2015;61:1144-6. https://www.ncbi.nlm.nih.gov/pubmed/26063717
Should I consider fosfomycin in the treatment of urinary tract infection in my male patient with suspected prostatitis?

Should I avoid intravenous furosemide for management of ascites in my patient with cirrhosis?

Generally, yes! IV furosemide for treatment of ascites in patients with cirrhosis should be avoided for couple of reasons.

First, in contrast to patients with congestive heart failure in whom the absorption of oral furosemide may be impaired due to bowel wall edema, patients with cirrhosis and ascites appear to absorb oral furosemide efficiently, similarly to that of control patients.1   Another reason for avoiding IV furosemide in this setting is the possibility of a significant drop in the GFR with its attendant rise in BUN and serum creatinine, clinically resembling a picture of hepatorenal syndrome.2

Although the mechanism of the adverse effect of IV furosemide on the renal function of patients with cirrhosis is not totally clear, furosemide-induced vasoconstriction, not intrasvascular volume depletion due to sodium wasting, seems to play an important role.3

Nevertheless, certain situations may necessitate the use of IV furosemide in patients with cirrhosis and ascites, such as in single doses to help identify patients who will be responsive to diuretics, and in patients in need of prompt diuresis such as those with concurrent pulmonary edema. In a somewhat reassuring study, a single dose of 80 mg IV furosemide reliably identified cirrhotic patients with ascites responsive to diuretics, without a significant risk of deteriorating renal function.3

 

References

  1. Sawhney VK, Gregory PB, Swezey SE, et al. Furosemide disposition in cirrhotic patients. Gastroenterology 1981; 81: 1012-16. https://www.ncbi.nlm.nih.gov/pubmed/7286579
  2. Daskalopoulos G, Laffi G, Morgan T, et al. Immediate effects of furosemide on renal hemodynamics in chronic liver disease with ascites. Gastroenterology 1987;92:1859-1863. https://www.ncbi.nlm.nih.gov/pubmed/3569760
  3. Spahr, L., Villeneuve, J., Tran, H. K., & Pomier-Layrargues, G. Furosemide-induced natriuresis as a test to identify cirrhotic patients with refractory ascites. Hepatology 2001;33:28-31. https://www.ncbi.nlm.nih.gov/pubmed/11124817

 

Contributed by Sam Miller, MD, Mass General Hospital, Boston, MA.

 

Should I avoid intravenous furosemide for management of ascites in my patient with cirrhosis?

My patient with cirrhosis has a large right sided pleural effusion with only a small amount of ascites. Could this effusion still be related to his cirrhosis?

Yes! Although we often associate pleural effusions in patients with cirrhosis with the presence of large ascites, some patients present with hepatic hydrothorax even in the absence of significant ascites.1-3  

In fact, in a study involving 77 patients with hepatic hydrothorax, 49% had minimal or small and 9% had no detectable ascites!1  Interestingly, nearly three-quarters of patients in this study had right sided pleural effusion with 10% having bilateral and 17% having left sided effusion only. Hepatic hydrothorax without ascites as the first sign of liver cirrhosis has also been reported.2

Although the mechanism(s) behind hepatic hydrothorax is not fully clear, the passage of peritoneal fluid into the pleural cavity through defects in the tendinous portion of the diaphragm assisted by negative intrathoracic pressure during inspiration is commonly favored. 1-3  

Supportive evidence includes a number of studies involving intraperitoneal injection of air, dyes or technetium 99 m-sulfur colloid that have demonstrated the trans-diaphragmatic flow of ascites into the pleural cavity. 1-4  In the absence of ascites, a complete equilibrium between the amount of ascites produced and its flow into and reabsorption by the pleural cavity is assumed.1,2

Bonus Pearl: Did you know that although most patients with hepatic hydrothorax have a transudative pleural effusion according to Light’s criteria, 1 study showed that 18% of patients may meet the Light’s criteria for an exudative effusion? 5,6

References

  1. Badillo R, Rockey DC. Hepatic hydrothorax: Clinical features, management, and outcomes in 77 patients and review of the literature. Medicine 2014;93:135-142. https://www.ncbi.nlm.nih.gov/pubmed/24797168
  2. Kim JS, Kim CW, Nam HS, et al. Hepatic hydrothorax without ascites as the first sign of liver cirrhosis. Respirology Case Reports 2016;4:16-18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4722098/
  3. Rubinstein D, McInnes IE, Dudley FJ. Hepatic hydrothorax in the absence of clinical ascites: diagnosis and management. Gastroenterology 1985;88:188-91. https://www.ncbi.nlm.nih.gov/pubmed/3964765
  4. Holt KA, Oliviera E, Rohatgi PK. Hepatic hydrothorax demonstration by Tc-99 sulfur colloid ascites scan. Clin Nucl Med 1999;24:609. https://www.ncbi.nlm.nih.gov/pubmed/10439187 
  5. Light RW. New treatment for hepatic hydrothorax? Ann Am Thorac Soc 2016;13:773-74. https://www.atsjournals.org/doi/full/10.1513/AnnalsATS.201603-223ED
  6. Bielsa S, Porcel JM, Castellote J, et al. Solving the Light’s criteria misclassification rate of cardiac and hepatic transudates. Respirology 2012;17”721-726. https://www.ncbi.nlm.nih.gov/pubmed/22372660
My patient with cirrhosis has a large right sided pleural effusion with only a small amount of ascites. Could this effusion still be related to his cirrhosis?

How does excess licorice consumption cause hypertension and hypokalemia?

The active ingredient of licorice, glycyrrhizic acid or glycyrrhizin, is first converted to glycyrrhetinic acid (GRA) in the bowel which is then absorbed. Once in the circulation, GRA inhibits activation of 11 β-hydroxysteroid dehydrogenase 2 (11 β-HSD2), an enzyme in renal tissue that converts active cortisol to inactive cortisone. Without the full action of this enzyme, proper sodium and potassium homeostasis would be difficult because cortisol is just as effective in stimulating mineralocorticoid receptors as aldosterone but with 100-1000 times higher concentration than that of aldosterone! 1-3

Other ways that GRA may cause hypertension and hypokalemia include inhibition of 5 β-reductase in the liver, an enzyme that metabolizes aldosterone and direct stimulation of mineralocorticoid receptors, though overall these mechanisms may not be as important as the effect of GRA on cortisol metabolism in renal tissue.1,2

Besides causing fluid retention, licorice ingestion has also been found to increase systemic vascular resistance possibly by increasing vascular tone and remodeling of the vascular wall, potentiating the vasoconstrictor actions of angiotensin II and catecholamines in smooth muscle, and suppressing vasodilatory systems, including endothelial nitric oxide synthase and prostacyclin synthesis.

It’s no wonder that the FDA issued a statement in 2017: “If you’re 40 or older, eating 2 ounces of black licorice a day for a day for at least two weeks could land you in the hospital with an irregular heart rhythm or arrhythmia.” 5

Bonus Pearl: Did you know that as early as 1951, extract of licorice was reported for treatment of Addison’s disease, a combination of licorice and soy sauce has been reported to be “life-saving” in a patient with Addison’s disease (2007), and GRA food supplementation may lower serum potassium in chronic hemodialysis patients (2009)? 6,7

 

References

  1. Sontia B, Mooney J, Gaudet L, et al. Pseudohyperaldosteronism, liquorice and hypertension. J Clin Hypertens (Greenwich) 2008; 10:153-57. https://www.ncbi.nlm.nih.gov/pubmed/18256580
  2. Omar HR, Komarova I, El-Ghonemi M, et al. Licorice abuse: time to send a warning message. The Adv Endocrinol Metab 2012;3:125-138. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3498851/
  3. Penninkilampi R, Eslick EM, Eslick GD. The association between consistent licorice ingestion, hypertension and hypokalaemia: as systematic review and meta-analysis. Journal of Human Hypertension 2017;31:699-707. https://www.ncbi.nlm.nih.gov/pubmed/28660884
  4. Black licorice: trik or treat? https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm 277152.htm
  5. Hautaniemi EJ, Tahvanainen AM, Koskela JK, et al. Voluntary liquorice ingestion increases blood pressure via increased volume load, elevated peripheral arterial resistance, and decreased aortic compliance. Sci Rep 2017;7:10947. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5591274/
  6. Groen J, Pelser H, Willebrands AF, et al. Extract of licorice for the treatment of Addison’s disease. N Engl J Med 1951;244:471-75. https://www.ncbi.nlm.nih.gov/pubmed/14806786
  7. Cooper H, Bhattacharya B, Verma V, et al. Liquorice and soy sauce, a life-saving concoction in a patient with Addison’s disease. Ann Clin Biochem 2007;44:397-99. https://www.ncbi.nlm.nih.gov/pubmed/17594790
  8. Farese S, Kruse Anja, Pasch A, et al. Glycyrrhetinic acid food supplementation lowers serum potassium concentration in chronic hemodialysis patients. Kidney International 2009;76:877-84. https://www.ncbi.nlm.nih.gov/pubmed/19641483
How does excess licorice consumption cause hypertension and hypokalemia?

My patient with chronic pain complains of difficulty sleeping. Would improving her sleep hygiene impact her pain medication requirement?

Most likely!

We should routinely assess for poor sleep as a potential impediment to adequate pain control in our patients. Substantial research supports a bidirectional relationship between pain and sleep.  That is, not only can pain disrupt sleep but sleep quality can also adversely affect pain.1   In fact, even a short-term disturbance in a stable sleep pattern may lower the pain threshold 2 and the ability to tolerate previously controlled pain.3

These observations are thought to result from activated stress responses from poor sleep hygiene which in turn produce cellular oxidative stress and inflammation of tissues and the nervous system. 4 This process can result in a vicious cycle between increasing pain and persistent insomnia.4,5  Breaking this cycle can reduce pain and improve function, among other desired outcomes.

Ongoing insomnia may also be a sign of a variety of other conditions that should be treated, such as mood disorder and sleep apnea. For example, besides standard non-pharmaceutical measures to improve sleep hygiene, continuous positive air pressure (CPAP) can reduce pain and opioid use in the setting of sleep apnea .2,6

Remember also that controlling pain with opioids in hopes of improving sleep may be counterproductive as opioids can contribute to sleep apnea.7,8  Melatonin may be a better sleep aid in this setting. 9

References

  1. Wei Y, Blanken TF, Van Someren EJW. Insomnia really hurts: effect of a bad night’s sleep on pain increases with insomnia severity. Front Psychiatry 2018;9:377. doi: 10.3389/fpsyt.2018.00377. https://www.ncbi.nlm.nih.gov/pubmed/30210367
  2. Charokopos A, Card ME, Gunderson C, Steffens C, Bastian LA. The association of obstructive sleep apnea and pain outcomes in adults: a systematic review. Pain Med 2018;19(suppl_1):S69-S75. doi: 10.1093/pm/pny140. https://www.ncbi.nlm.nih.gov/pubmed/30203008
  3. Sivertsen B, Lallukka T, Petrie KJ, et al. Sleep and pain sensitivity in adults. Pain. 2015;156:1433-9. https://www.ncbi.nlm.nih.gov/pubmed/25915149
  4. Iacovides S, George K, Kamerman P, Baker FC. Sleep fragmentation hypersensitizes healthy young women to deep and superficial experimental pain. J Pain. 2017;18:844-854. doi: https://doi.org/10.1016/j.jpain.2017.02.436. https://www.ncbi.nlm.nih.gov/pubmed/28300651
  5. Edwards RR, Almeida DM, Klick B, Haythornthwaite JA, Smith MT. Duration of sleep contributes to next-day pain report in the general population. Pain. 2008;137:202-7. doi: 10.1016/j.pain.2008.01.025. https://www.ncbi.nlm.nih.gov/pubmed/18434020
  6. Edwards RR, Almeida DM, Klick B, Haythornthwaite JA, Smith MT. Duration of sleep contributes to next-day pain report in the general population. Pain. 2008 Jul;137(1):202-7. doi: 10.1016/j.pain.2008.01.025. https://www.ncbi.nlm.nih.gov/pubmed/18434020
  7. Marshansky S, Mayer P, Rizzo D, Baltzan M, Denis R, Lavigne GJ. Sleep, chronic pain, and opioid risk for apnea. Prog Neuropsychopharmacol Biol Psychiatry 2018 20;87:234-244. https://www.ncbi.nlm.nih.gov/pubmed/28734941
  8. Jungquist CR, Flannery M, Perlis ML, Grace JT. Relationship of chronic pain and opioid use with respiratory disturbance during sleep. Pain Manag Nurs 2012;13:70-9. doi: 10.1016/j.pmn.2010.04.003. https://www.ncbi.nlm.nih.gov/pubmed/22652280
  9. Landis CA. Is melatonin the next “new” therapy to improve sleep and reduce pain? Sleep 2014; 37: 1405–1406. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4153056/

Contributed by Paul Arnstein, PhD, RN, FAAN, Mass General Hospital, Boston, MA.

My patient with chronic pain complains of difficulty sleeping. Would improving her sleep hygiene impact her pain medication requirement?

Does erythrocyte sedimentation rate (ESR) have diagnostic utility in my patient with chronic renal failure?

Short answer: No! This is because most studies have shown frequently high ESR’s in stable “uninflamed” patients with chronic renal failure (CRF) (including those on dialysis) at levels often associated with infection, connective tissue disease, or malignancy in normal renal function. 1-4  

In fact, in a study involving patients with CRF, 57% of patients had markedly elevation of ESR (greater than 60 mm/h), with 20% having ESR greater than 100 mm/h; type or duration of dialysis had no significant effect on ESR levels.1 Another study reported a specificity for abnormal ESR of only 35% for commonly considered inflammatory conditions (eg, infections or malignancy) among patients with CRF. 2

But is it the chronic inflammation in diseased kidneys or the uremic environment that elevates ESR? A cool study compared ESR in CRF in patients who had undergone bilateral nephrectomies with those with retained kidneys and found no significant difference in the ESR between the 2 groups. 4  So it looks like it’s the uremic environment, not diseased kidneys themselves that result in elevated ESR in these patients.

The mechanism behind these observations seem to reside entirely within the patients’ plasma, not the erythrocytes. Within the plasma, fibrinogen (not gammaglobulins) seem to be the most likely factor explaining elevated ESR among patients with CRF. 1,2

Bonus pearl:  Did you know that ESR is nearly 100 years old, first described in 1921? 5

References

  1. Barthon J, Graves J, Jens P, et al. The erythrocyte sedimentation rate in end-stage renal failure. Am J Kidney Dis 1987;10: 34-40. https://www.ncbi.nlm.nih.gov/pubmed/3605082
  2. Shusterman N, Morrison G, Singer I. The erythrocyte sedimentation rate and chronic renal failure. Ann Intern Med 1986;105:801. http://annals.org/aim/fullarticle/700910
  3. Arik N, Bedir A, Gunaydin M, et al. Do erythrocyte sedimentation rate and C-reactive protein levels have diagnostic usefulness in patients with renal failure? Nephron 2000;86:224. https://www.ncbi.nlm.nih.gov/pubmed/11015011
  4. Warner DM, George CRP. Erythrocyte sedimentation rate and related factors in end-stage renal failure. Nephron 1991;57:248. https://www.karger.com/Article/PDF/186266
  5. Fahraeus R. The suspension stability of the blood. Acta Med Scan 1921;55:70-92. https://onlinelibrary.wiley.com/doi/abs/10.1111/j.0954-6820.1921.tb15200.x

 

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Does erythrocyte sedimentation rate (ESR) have diagnostic utility in my patient with chronic renal failure?

My patient with cirrhosis has hypohonia and cogwheel rigidity. Is there a connection between cirrhosis and Parkinson’s disease?

There is a high prevalence of extra-pyramidal or Parkinson-like (PL) clinical findings in patients with cirrhosis. In fact, over 75% of patients with cirrhosis may exhibit PL signs, such as tremor, rigidity, and akinesia, with 88% also showing hyperintensity in the globus pallidus of basal ganglia on T1-weighted brain MRI.1

What’s even more interesting is the similarity between PL clinical and MRI findings among patients with cirrhosis and those with Manganese (Mn) toxicity.2,3 More specifically, similar MRI findings involving the globus pallidus have been reported in Mn-exposed workers, patients with cirrhosis, and those undergoing total parenteral nutrition with excessive Mn replacement. 4 These observations seem more than coincidental as 67% of patients with cirrhosis have been reported to have elevated blood Mn concentrations, with significantly higher levels in patients with previous portacaval anastomoses or transjugular intrahepatic portosystemic shunt (TIPS).1

Mn-induced parkinsonism is distinguishable from classic Parkinson’s disease in several ways, including the absence of Lewy bodies, more frequent dystonia, and less resting tremor.5 Also, remember that Mn-induced PL disease does NOT respond to L-dopa, a drug used to treat early stages of PD. 5 This finding can be explained by the fact that, in contrast to Parkinson’s disease where many of the dopamine-producing cells in the substantia nigra of the brain degenerate resulting in dopamine deficiency, in Mn-induced PL disease the problem is release of dopamine into synapses not its production.5

Bonus Pearl: Did you know that due to its paramagnetic properties, manganese can be effectively seen by MRI!

References

  1. Spahr L, Butterworth RF, Fontaine S, et al. Increased blood manganese in cirrhotic patients: relationship to pallidal m agnetic resonance signal hyperintensity and neurological symptoms. Hepatology 1996;24:1116-1120. https://www.ncbi.nlm.nih.gov/pubmed/8903385
  2. Hauser RA, Zesiewicz TA, Rosemurgy AS, et al. Manganese intoxication and chronic liver failure. Ann Neurol 1994;36:871-75. https://www.ncbi.nlm.nih.gov/pubmed/7998773
  3. Krieger S, Jaub M, Jansen O, et al. Neuropsychiatric profile and hyperintense globus pallidus on T1-weighted magnetic resonance images in liver cirrhosis. Gastroenterol 1996;111:147-55. https://www.ncbi.nlm.nih.gov/pubmed/8698193
  4. Lucchini R, Albini E, Placidi D, et al. Brain magnetic resonance imaging and manganese exposure. Neurotoxicity 2000;21:769-75. https://www.ncbi.nlm.nih.gov/pubmed/11130281
  5. Kwakye GF, Paoliello MMB, Mukhopadhyay S, et al. Manganese-induced parkinsonism and Parkinson’s disease: Shared and distinguishable features. Int J Environ Res Public Health 2015;12;7519-40. https://www.ncbi.nlm.nih.gov/pubmed/26154659

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My patient with cirrhosis has hypohonia and cogwheel rigidity. Is there a connection between cirrhosis and Parkinson’s disease?

Why is latent tuberculosis usually treated with one antibiotic while active tuberculosis is treated with 2 or more drugs?

Conventional wisdom has been that in active tuberculosis (TB) patients harbor large numbers of replicating Mycobacterium tuberculosis (Mtb), requiring multiple antibiotics to prevent the emergence of resistant mutants. In contrast, Mtb under latent or “inactive” conditions is presumed to have little capacity for mutation due to reduced bacterial replication, thus generally requiring only one antibiotic for preventive therapy.1

However, the assumption that Mtb has a low capacity for mutation in latent TB due to slow bacterial replication has been challenged in recent years. An experimental study in macaque monkeys with latent Mtb infection using whole genome sequencing demonstrated that despite reduced replication, Mtb acquires a similar number of chromosomal mutations during latency as it does during active infection.1

This finding supports the more current and evolving concept of latent TB which assumes diverse mycobacterial growth states, ranging from complete absence of organisms to actively replicating bacterial populations.2 It also explains why, although effective, isoniazid monotherapy may be a risk factor for the emergence of INH resistance in latent TB. 1,3

 Bonus Pearl: Did you know that INH treatment of latent TB in adults is 60-80% protective when given for 6 months, and 90% protective when given for 9 months? 4

References

  1. Ford CB, Lin PL, Chase M, et al . Use of whole genome sequencing to estimate the mutation rate of Mycobacterium tuberculosis during latent infection. Nat Genet. 2011;43:482-86. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3101871/
  2. Gideon HP, Flynn JL. Latent tuberculosis: what the host “sees”? Immunol Res 2011;50:202-12. https://www.ncbi.nlm.nih.gov/pubmed/21717066
  3. Balcells ME, Thomas SL, Faussett PG, et al. Isoniazid preventive therapy and risk for resistant tuberculosis. Emerg Infect Dis 2006;12:744-51. https://www.ncbi.nlm.nih.gov/pubmed/16704830
  4. Piccini P, Chiappini E, Tortoli E, et al. Clinical peculiarities of tuberculosis. BMC Infect Dis 2014; 14 (Suppl 1):S4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4015485/

 

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Why is latent tuberculosis usually treated with one antibiotic while active tuberculosis is treated with 2 or more drugs?