Thyroid is one of the largest endocrine glands found in the neck, below the Adam's Apple with the function of regulating the body use of energy, make of proteins by producing its hormones as a result of the stimulation of thyroid-stimulating hormone (TSH) produced by the anterior pituitary.
Thyroid disease is defined as a condition of malfunction of thyroid. Hyperthyroidism is a condition in which the thyroid gland is over active and produces too much thyroid hormones. Hypothyroidism is a condition in which the thyroid gland is under active and produces very little thyroid hormones. Thyroid cancer is defined as condition in which the cells in the thyroid gland have become cancerous.
Thyroid hormone resistance syndrome
Thyroid hormone resistance syndrome is defined as a condition of which affected individuals have elevated serum thyroid hormone levels and inappropriately normal or elevated thyroid-stimulating hormone (TSH) but are usually clinically euthyroid and require no treatment. Selective pituitary resistance to thyroid hormone (PRTH) is characterized by resistance in the pituitary gland but not in peripheral tissues(a).
A. Symptoms
1. hyperactivity, emotional lability, a below average intelligence quotient, and short stature
Thyroid hormone resistance mutations are associated with a wide variety of phenotypes and subsequent treatment challenges. Among the more common symptoms are hyperactivity, emotional lability, a below average intelligence quotient, and short stature(1).
2. Hyperthyroid symptoms
There is a first case report of a resistance to thyroid hormone in a neonate presenting with hyperthyroid symptoms born to a mother with Graves' disease and treated with methimazole and iodine(2). such as Sudden weight loss, rapid heartbeat (tachycardia), increased appetite, nervousness, anxiety and irritability, tremor, etc(3).
3. Psychiatric disorders
There is a report of six children from five unrelated families with esistance to thyroid hormone (RTH). All patients grew normally and presented variable symptoms that were treated according to need. Two patients developed psychiatric disorders. Only one of the four affected parents exhibited clinical signs of RTH (tachycardia and depression)(4).
4. Other symptoms
According to the study by the Northwestern University Medical School,, clinical effects of RTH can include short stature, delayed bone maturation, hyperactivity, learning disabilities, and hearing defects, as well as variable features of hyper- and hypothyroidism(5). Others indicated that RTH symptoms include failure to thrive, growth retardation and attention-deficit hyperactivity disorder in childhood, and goitre and thyrotoxic cardiac symptoms in adults(5a).
B. Causes
Genetic mutation
Thyroid hormone resistance occurs when a genetic mutation in the thyroid hormone receptor leads to reduced hormone binding affinity; the concentration of free thyroid hormone in the circulation is inversely correlated with the hormone binding affinity of the mutant receptor(6), such as mutation in the THRbeta gene, A317T(7) and E333D(8). According to the study of Syndromes of reduced sensitivity to thyroid hormone: genetic defects in hormone receptors, cell transporters and deiodination by the University of Chicago, Mutations in MCT8 and SECISBP2 have also been associated with this condition(9) and a patient with the unusual coincidence of two rare congenital disorders, lingual ectopy of the thyroid gland and resistance to thyroid hormone (RTH), resulting in impaired thyroid hormone production and action, respectively(10). Thyroid hormone resistance syndrome affect approximately 1 in 40,000 live births and of of which over 100 different mutations have been identified.
B.2. Risk factors
1. Dominant inheritance
Resistance to thyroid hormone (RTH) is an inherited syndrome of reduced tissue responsiveness to thyroid hormone. To date, all individuals expressing the RTH phenotype have been found to harbor mutations in the thyroid hormone receptor beta (TR beta) gene that impair T3-mediated function(11). Others reported a baby at age 70 days, an R243W mutation in thyroid hormone receptor β was detected in our patient; while absent in his mother, the mutation was present in his father, who never showed any symptoms(12).
2. Graves' disease
Resistance to thyroid hormone is a syndrome caused by thyroid hormone receptor β mutations, which are usually inherited in an autosomal-dominant pattern. There is a report of a resistance to thyroid hormone in a neonate presenting with hyperthyroid symptoms born to a mother with Graves' disease and treated with methimazole and iodine(12).
3. Minor alterations at the DNA level
Mutations in the thyroid hormone receptor (TR) beta gene are responsible for RTH and 122 different mutations have now been identified belonging to 300 families. With the exception of one family found to have complete deletion of the TRbeta gene, all others have been demonstrated to have minor alterations at the DNA level, according to the study by the Stoke Mandeville Hospital(13).
C. Complications and diseases associated to Thyroid hormone resistance
C.1. Complications
1. Growth retardation/short stature and skeletal dysplasia
There is a report of a first human cases (female, age 6 y; father and daughter, ages 47 and 11 y, respectively) with growth retardation/short stature, skeletal dysplasia, constipation, and defective thyroid receptor α (TRα)(14).
2. Thyroxine excess and inappropriate TSH secretion
Resistance to thyroid hormone (RTH) is an uncommon inherited cause of hyperthyroxinemia with inappropriate TSH secretion, according to the study by the University of Cambridge, Addenbrooke's Hospital, United Kingdom(15).
3. Cardiovascular risk
RTH patients show evidence in this study of increased augmentation index consistent with an increase in arterial stiffness compared with euthyroid controls. They also demonstrate elevated LDL-cholesterol levels. Both these measures may lead to increased cardiovascular risk(16).
C.2. Diseases associated to Thyroid hormone resistance
1. Differentiated thyroid cancer (DTC)
There are reports of four unusual cases of DTC associated with TSHoma (2 cases), RTH (1 case), and an elevated TSH of unknown etiology (1 case)(17).
2. A pituitary tumor
There is a report of a woman in whom the standard evaluation for inappropriate TSH secretion was insufficient to distinguish these entities. The patient had a low-normal TRH stimulation test and an unmeasurable alpha-glycoprotein subunit level; however, a pituitary magnetic resonance imaging (MRI) revealed an adenoma. More testing using a T3 suppression test supported a RTH diagnosis and a R438H mutation was found in the TR-beta gene. To our knowledge, this represents the first report of an apparently incidental pituitary adenoma in the setting of documented resistance to thyroid hormone. As such, it raises the question of whether RTH predisposes to pituitary hyperplasia and adenoma. development(18).
3. Papillary thyroid carcinoma
There is an association of thyroid hormone resistance syndrome and papillary thyroid carcinoma(19).
4. Immune thrombocytopenic purpura (ITP)
There is a report of a 9-year-old girl presented with ITP and features of hypothyroidism in the form of goiter and growth retardation. She was subsequently found to have RTH. High-dose thyroid hormone replacement was required to overcome the resistance that not only ameliorated the features of hypothyroidism but also brought an apparent remission of ITP(20).
5. Postpartum thyroiditis
there is a repopt of a report of a unique case of a woman affected by RTH, due to a novel mutation V283A in THRB, who experienced PPT with a severe thyrotoxic phase after both her pregnancies. The association between RTH and PPT has never been reported in the literature. In particular, the marked suppression of TSH occurring when levels of TH are particularly elevated is not a frequent condition during RTH(21).
6. Chronic thyroiditis
There is a report of the five-year medical history of a Japanese woman and her father with RTH and coincidental chronic thyroiditis(22).
D. Misdiagnosis and Diagnosis
D.1. Misdiagnosis
1. Hyperthyroidism
There is a report of an isolated case of RTH initially misdiagnosed as hyperthyroidism, and detail the investigations which ultimately led to the correct diagnosis(23).
2. Falsely diagnnosis
There is a report of a 63-year-old woman was referred because of suspected SITSH. Laboratory tests showed a normal TSH (0.52 μIU/L; normal range: 0.5-5.0) measured by sandwich Elecsys, and elevated FT4 (3.8 ng/dL; normal range: 0.9-1.6) and FT3 (7.6 pg/mL; normal range: 2.3-4.0), determined by competitive Elecsys. To exclude possible assay interference, aliquots of the original samples were retested using a different method (ADVIA Centaur), which showed normal FT4 and FT3 levels. Eight hormone levels, other than thyroid function tests measured by competitive or sandwich Elecsys, were higher or lower than levels determined by an alternative analysis. Subsequent examinations, including gel filtration chromatography, suggested interference by substances against ruthenium, which reduced the excitation of ruthenium, and resulted in erroneous results(24). Other suggested that patients with TSH-secreting pituitary tumors(TSHoma) also manifest SITSH. Thus, the differential diagnosis of RTH vs. TSHoma is sometimes difficult and challenging. In this review article, the etiology of RTH and diagnostic approach for SITSH are explained and an algorithm for differential diagnosis of RTH vs. TSHoma is proposed(25).
3. Coexistence of mutation genes
There is a report of the coexistence of THRB and TBG gene mutations in the same individual (mother of the proband), whereas other affected family members had only 1 of the 2 genes mutated. The case illustrates the difficulty that might be encountered in the interpretation of thyroid function tests when different genetic defects affecting thyroid function coexist(26).
4. Grave's disease
RTH is often misdiagnosed as Graves' disease. However, these disorders can coexist, and the concurrent presence of both disorders in a patient can present diagnostic challenges. A previous report of a patient with Graves' disease associated with RTH was published before gene sequencing could be used to confirm diagnosis of RTH. There is a report of a patient with Graves' disease and concurrent RTH that was confirmed by gene sequencing, showing a mutation in the thyroid hormone receptor beta gene(27).
D.2. Diagnosis
If you are experience certain symptoms of the above and your doctor suspects that you have developed acute thyroiditis, after recording the past and present history and completing a physical exam, the tests which your doctor orders may include
1. Urinary test
Urinary cortisol metabolites are altered both quantitatively and qualitatively in thyroid dysfunction. According to the study by the Showa University, the ratio of the urinary concentrations of cortisol metabolites, THE/THF, appears to be a good marker for peripheral thyroid hormone resistance(28).
2. Blood test
Unfortunately, the blood test results of the disorder can also be found in other disorders such as TSH-oma (pituitary adenoma), or other pituitary disorders. According to the study by the Nagoya University, almost all patients with RTH manifest unsuppressed thyrotropin (TSH) despite elevated free-T4 and free-T3 levels. This abnormal finding in the thyroid function test is termed "syndrome of inappropriate secretion of TSH" (SITSH) or "central hyperthyroidism". Patients with TSH-secreting pituitary tumors(TSHoma) also manifest SITSH. Thus, the differential diagnosis of RTH vs. TSH-oma is sometimes difficult and challenging(29)
3. Identifying a mutation of the thyroid receptor
Resistance to thyroid hormone (RTH) is a rare condition usually diagnosed in patients with classic thyroid function tests (TFTs) of elevated thyroid hormone levels with nonsuppressed TSH. According to the study by the, At least six major steps are required for secreted thyroid hormone (TH) to exert its action on target tissues. Mutations interfering with three of these steps have been so far identified. The first recognized defect, which causes resistance to TH, involves the TH receptor β gene and has been given the acronym RTH(30).
E. Treatments
E.1. In conventional medicine perspective
1. The table
Table. Suggested therapeutic approaches for resistance to thyroid hormone (RTH) patients.
| ___________________________________________________________________ | |
| Drugs | Untoward effects and limitations |
| ___________________________________________________________________ | |
| TRIAC | Effective in almost all patients |
| D-T4 | Effective in almost all patients |
| T3 | Production of daily peaks of very high T3 concentrations, which |
| contribute to maintain clinical hyperthyroidism | |
Bromocriptine | Transient effect owing to TSH escape from inhibition |
| Sms analog | Transient effect owing to TSH escape from inhibition |
| Corticosteroid | Cause of severe inhibition of hypothalamic-pituitary-adrenal axis function and cushingoid features |
| Antithyroid drugs | Cause of further increase in TSH circulating level with consequent increase of goiter size and to hyperplasia at pituitary thyrotroph level |
| b-blockers | Effects limited to b-adrenergic blockade. Propranolol inhibits peripheral conversion of T4 to T3, causing a worsening of tissue hypometabolic state. Cardiac selective compounds, such as atenolol devoid of effect on peripheral T4 conversion, appear to be more useful(31). |
2. Limitation
According to the study by the Fitzsimons Army Medical Center, the thyroid hormone resistance syndromes are disorders in which the body's tissues are resistant to the effects of thyroid hormone. Generalized resistance to thyroid hormone (GRTH) is characterized by resistance in the pituitary gland and in most or all of the peripheral tissues. Affected individuals have elevated serum thyroid hormone levels and inappropriately normal or elevated thyroid-stimulating hormone (TSH) but are usually clinically euthyroid and require no treatment. Selective pituitary resistance to thyroid hormone (PRTH) is characterized by resistance in the pituitary gland but not in peripheral tissues. Patients have elevated serum thyroid hormone levels and normal or elevated TSH levels and are clinically thyrotoxic. Therapy is usually necessary, but current choices are not completely satisfactory. Selective peripheral resistance to thyroid hormone (PerRTH) is characterized by resistance in peripheral tissues but not in the pituitary. The only patient thus far described had normal serum thyroid hormone and TSH levels but was clinically hypothyroid and improved with thyroid hormone administration. All of these disorders are probably more common than is generally recognized and are often misdiagnosed and inappropriately treated. GRTH, in most cases studied, results from a mutation in the thyroid hormone receptor beta gene causing an amino acid substitution in or a partial or complete deletion of the thyroid hormone-binding domain of the receptor. The causes of PRTH and PerRTH remain to be determined(32). Other studies indicated that in this age of rapidly advancing knowledge, it is reasonable to expect that the not too distant future will bring specific treatments for RTH. This will probably not be in the form of gene therapy as the dominant expression would require excision of the defective gene. The most simple genetic approach, one within the realm of current technology, is the selection of an oocyte from the affected mother that does not harbor the abnormal allele for in vitro fertilization followed by implantation into the donor. This insures a fetus without RTH but does not guarantee a normal pregnancy and fetal development. The development of TH agonists and antagonists that are TR-isoform specific would allow the stimulation or blockade of specific tissue effects that are perturbed in a given individual with RTH(33).
Sources
(a) http://www.ncbi.nlm.nih.gov/pubmed/8475937
(1) http://www.ncbi.nlm.nih.gov/pubmed/18622209
(2) http://www.ncbi.nlm.nih.gov/pubmed/22905724
(3) http://www.ncbi.nlm.nih.gov/pubmed/20151830
(4) http://www.ncbi.nlm.nih.gov/pubmed/21870171
(5) http://www.ncbi.nlm.nih.gov/pubmed/8594618
(5a) http://www.ncbi.nlm.nih.gov/pubmed/9350446
(6) http://www.ncbi.nlm.nih.gov/pubmed/18622209
(7) http://www.ncbi.nlm.nih.gov/pubmed/19227423
(8) http://www.ncbi.nlm.nih.gov/pubmed/17177139
(9) http://www.bprcem.com/article/S1521-690X%2807%2900026-7/abstract
(10) http://www.ncbi.nlm.nih.gov/pubmed/16053391
(11) http://www.ncbi.nlm.nih.gov/pubmed/8954015
(12) http://www.ncbi.nlm.nih.gov/pubmed/22905724
(13) http://www.ncbi.nlm.nih.gov/pubmed/17132274
(14) http://www.ncbi.nlm.nih.gov/pubmed/23940126
(15) http://www.ncbi.nlm.nih.gov/pubmed/7998483
(16) http://www.ncbi.nlm.nih.gov/pubmed/18803680
(17) http://www.ncbi.nlm.nih.gov/pubmed/23553855
(18) http://www.ncbi.nlm.nih.gov/pubmed/11327621
(19) http://www.ncbi.nlm.nih.gov/pubmed/23457315
(20) http://www.ncbi.nlm.nih.gov/pubmed/23382302
(21) http://www.ncbi.nlm.nih.gov/pubmed/23134553
(22) http://www.ncbi.nlm.nih.gov/pubmed/16723809
(23) http://www.ncbi.nlm.nih.gov/pubmed/16445164
(24) http://www.ncbi.nlm.nih.gov/pubmed/22673200
(25) http://www.ncbi.nlm.nih.gov/pubmed/23214067
(26) http://www.ncbi.nlm.nih.gov/pubmed/23633200
(27) http://www.ncbi.nlm.nih.gov/pubmed/20151830
(28) http://www.ncbi.nlm.nih.gov/pubmed/8257864
(29) http://www.ncbi.nlm.nih.gov/pubmed/23214067
(30) http://www.bprcem.com/article/S1521-690X%2807%2900026-7/abstract
(31) http://www.hotthyroidology.com/editorial_79.html
(32) http://www.ncbi.nlm.nih.gov/pubmed/8475937
(33) http://jcem.endojournals.org/content/84/2/401.full
Euthyroid sick syndrome
Euthyroid sick syndrome is defined as a condition of low T3 low T4 syndrome. According ot the study by the Mayo Clinic, in other word this is the abnormalities of thyroid hormone concentrations seen commonly in a wide variety of nonthyroidal illnesses, resulting in low triiodothyronine, total thyroxine, and thyroid stimulating hormone concentrations(a). Decreased triiodothyronine (T3) levels are most common. Patients with more severe or prolonged illness also have decreased thyroxine (T4) levels. Serum reverse T3 (rT3) is increased. Patients are clinically euthyroid and do not have elevated thyroid-stimulating hormone (TSH) levels(b). Causes of euthyroid sick syndrome include a number of acute and chronic conditions, including pneumonia, fasting, starvation, sepsis, trauma, cardiopulmonary bypass, malignancy, stress, heart failure, hypothermia, myocardial infarction, chronic renal failure, cirrhosis, and diabetic ketoacidosis and inflammatory bowel disease(c). Others, in the study of classified SES into 3 subgroups according to the different alterations seen in the values of T3, T4, FT3, FT4, TSH, rT3 and TBG suggested that in SES type I the diseases seen, in order of frequency, were: obstructive chronic bronchopneumopathy with acute respiratory failure, diabetic ketoacidosis, neoplasms, ischemic heart disease, cardiac failure, chronic renal failure, liver diseases, acute cerebral vasculopathies, sepsis and collagenopathies. The disease seen in the 2 cases of SES type II was obstructive chronic bronchopneumopathy with acute respiratory failure. In SES type III the diseases seen were, in order of frequency: diabetic ketoacidosis, lung diseases, ischemic heart disease, cardiac failure, peripheral arteriopathies, acute cerebral vasculopathies, neoplasms, liver diseases, acute renal failure(d).
Euthyroid sick syndrome as a result of pneumonia
Pneumonia is defined as a condition of the inflammation of the lung as a result of infection, caused by bacteria, such as bacteria Streptococcus pneumoniae or influenza viruses in most cases. Fungi, such as Pneumocystis jiroveci, certain medication such as PPI Stomach Acid Drugs and other conditions such as impaired immune systems.
According to Author: V. Dimov, M.D. and S. Randhawa, M.D. There is report of a 57-year-old female with a past medical history (PMH) of SLE, hypertension (HTN) and depression was transferred from an outside hospital for work-up and treatment of a change in mental status and fever. That admission was preceded by a one-week history of diffuse joint pain, weakness, and fatigue. On transfer, she was diagnosed with multilobar pneumoni...(1).
1. Pneumonia - Viral causes of Pneumonia
2. Pneumonia - Bacterial causes of Pneumonia
3. Fungi and parasites causes of Pneumonia
4. Pneumonia - The Risk factors
5. Pneumonia - The Misdiagnosis
6. Pneumonia - Diseased associated to pneumonia
7. Pneumonia - The Complications
8. Pneumonia - The Diagnosis
9. Preventions
9.1. Pneumonia Preventions- The do and do not's list
9.2. Diet to prevent pneumonia
9. 3. Phytochemicals to prevent pneumonia
9.4. Antioxidants to prevent pneumonia
10. Treatments
10.1. Pneumonia Treatments In conventional medicine perspective
10.2. Pneumonia Treatments In Herbal medicine perspective
10.3. Pneumonia Treatments In traditional Chinese medicine perspective
Sepsis
Sepsis is defined as a condition caused by chemicals released into the bloodstream to fight the infection trigger inflammation throughout the body as a result of severe infection(a)(b). according to the study by the University of Utah, sepsis is the commonest cause of admission to medical ICUs across the world. Mortality from sepsis continues to be high. Besides shock and multi-organ dysfunction occurring following the intense inflammatory reaction to sepsis, complications arising from sepsis-related immunoparalysis contribute to the morbidity and mortality from sepsis(c).
A. Symptoms
1. Chilly periphery, fever, jaundice, platelet and hemoglobin
I(n the study to o explore the risk factors, clinical symptoms, hematological parameters, causative pathogen and antibiotic susceptibility of neonatal sepsis in a Chinese NICU, found that the clinical symptoms or laboratory results such as chilly periphery, fever, jaundice, platelet and hemoglobin also had between-group differences. The most common responsible pathogenic bacteria species present in EOS group was Coagulase-negative Staphylococcus (CoNS)(1).
2. Abnormalities of blood pressure, respiration, temperature, and heart rate, and less well-known changes in heart rate variability
Early detection of late-onset neonatal sepsis, before the onset of obvious and potentially catastrophic clinical signs, is an important goal in neonatal medicine. Sepsis causes a well-known series of physiologic changes including abnormalities of blood pressure, respiration, temperature, and heart rate, and less well-known changes in heart rate variability, according to the University of Virginia(2).
3. Significantly decreased urine output but accumulative fluid balance had a weak correlation with delta sequential organ failure assessment score (r = 0.32, P = 0.001) and lung injury score (r = 0.13, P = 0.02) and negative correlation with PaO2/FIO2 ratio (r = -0.28, P = 0.001)(3).
4. Abrupt change in mental status, difficult breathing and abnormal blood circulation
Early recognition of sepsis and septic shock in children relies on obtaining an attentive clinical history, accurate vital signs, and a physical examination focused on mental status, work of breathing, and circulatory status, according to the study by the University of Colorado School of Medicine(4).
B. Causes and Risk factors
B.1. Causes
1. Bacteria infection
In the study of Neonates admitted to the neonatal intensive care unit (NICU) at National Taiwan University Hospital (NTUH) between January 2001 and December 2006, found that in n early-onset sepsis, the most common pathogens responsible included group B streptococci (GBS) (36%) and Escherichia coli (E. coli) (26%). GBS was associated with more meningitis involvement but lower incidence of mortality compared with E. coli. The most common causative microorganisms in late-onset sepsis were coagulase-negative staphylococci (CONS) (40%) and Candida (15%). The sepsis-related mortality rates were higher in early-onset sepsis (10%) than in late-onset sepsis (7%)(5).
Other study indicated that Burkholderia cepacia has rarely been reported in Honolulu. Its emergence as a nursing home-acquired pathogen with high mortality rate is concerning. This case report describes a local nursing home patient who was diagnosed with B. cepacia sepsis in 2012(6).
2. Renal infection (Acute pyelonephritis (APN))
IOn the study to assess the risk factors for septic shock by multivariate logistic regression analysis of 69 patients with obstructive APN associated with upper urinary tract calculi who were admitted to the hospital, indicated that patients with obstructive APN associated with upper urinary tract calculi who have decreases in platelet count and serum albumin level should be treated with caution against the development of septic shock(7).
3. Pneumonia
Klebsiella (K.) pneumoniae is a common cause of pneumonia-derived sepsis, according to the study by the University of Amsterdam(8).
4. Bloodstream infection
In the study to determine the independent risk factors on mortality in patients with community-acquired severe sepsis and septic shock, found that in addition to the severity of illness, hypoalbuminemia was identified as the most important prognostic factor in community-acquired bloodstream infection with severe sepsis and septic shock(9).
5. Abdominal infection
In the study to investigate the alteration of complement system in patients with severe abdominal sepsis and evaluate the role of complement depletion in prognosis of such patients, indicated that complement C3 depletion was found to be connected to poor prognosis in severe abdominal sepsis. This depletion seems to be associated with coagulopathy and aggravated infection during sepsis, which should be paid close attention in critical care(10).
6. Dementia in elders
In the population-based cohort study, in analyzing 41,672 older (≥ 65 years) patients, including 3,487 (8.4%) with dementia, from the first-time admission claim data between 2005 and 2007 for a nationally representative sample of one million beneficiaries enrolled in the Taiwan National Health Insurance Research Database, found that In hospitalized older patients, the presence of dementia increased the risks of acute organ dysfunction, severe sepsis and hospital mortality. However, after intervention using life-support treatments, dementia only exhibited a minor role on short-term mortality(11).
7. Drug-resistant bacteria
In the study to identify the frequency of bacterial isolates in early-onset neonatal sepsis (EONS) and their antimicrobial resistance pattern, found that K. pneumoniae was the predominant causative bacteria of EONS followed by E. cloacae and E. coli. There was a high resistance to ampicillin. Imipenem had the maximum overall activity against the causative bacteria. Continuous surveillance is needed to monitor the changing epidemiology of pathogens and antibiotic sensitivity(12).
8. Weakened immune systems
Sepsis remains the leading cause of death in most intensive care units. Advances in understanding the immune response to sepsis provide the opportunity to develop more effective therapies. The immune response in sepsis can be characterized by a cytokine-mediated hyper-inflammatory phase, which most patients survive, and a subsequent immune-suppressive phase. Patients fail to eradicate invading pathogens and are susceptible to opportunistic organisms in the hypo-inflammatory phase. Many mechanisms are responsible for sepsis-induced immuno-suppression, including apoptotic depletion of immune cells, increased T regulatory and myeloid-derived suppressor cells, and cellular exhaustion(13).
B.2. Risk factors
1. Term infants, while very low birth weight (VLBW) and preterm infants
According to the study by the Taipei City Hospital, total of 109 episodes of sepsis were identified in 100 neonates. The incidence of sepsis was 4.06% among all NICU admissions. Most neonates with early-onset sepsis were term infants, while very low birth weight (VLBW) and preterm infants accounted for the majority of cases of late-onset sepsis(14).
2. Obesity, operative vaginal delivery and age <25 years
In the study to describe the risk of maternal sepsis associated with obesity and other understudied risk factors such as operative vaginal delivery, found that ontrolling for mode of delivery and demographic and clinical factors, obese women had twice the odds of uncomplicated sepsis (OR 2.12; 95% CI 1.14-3.89) compared with women of normal weight. Age <25 years (OR 5.15; 95% CI 2.43-10.90) and operative vaginal delivery (OR 2.20; 95% CI 1.02-4.87) were also significant predictors of sepsis. Known risk factors for maternal sepsis were also significant in this study (OR for uncomplicated and severe sepsis respectively): multiparity (OR 6.29, 12.04), anaemia (OR 3.43, 18.49), labour induction (OR 3.92 severe only), caesarean section (OR 3.23, 13.35), and preterm birth (OR 2.46 uncomplicated only)(15).
3. Elder
If you are elder, you are at increased risk of sepsis
4. Patient in intensive care and with weakened immune system
Intra-abdominal infections are a common problem for the general surgeon and major sources of morbidity and mortality in the intensive care unit(16). Other indicated that severe sepsis has emerged as a major cause of admission and mortality for hospitalized HIV/AIDS patients, significantly affecting short- and longer-term survival of critically ill HIV/AIDS patients(17).
5. Invasive devices
There is a study of indwelling intravenous polyethylene catheters as factors influencing the risk of microbial colonization and sepsis(18).
6. Obesity and alcpholism
A multivariate analysis revealed that obesity (adjusted odds ratio [aOR] 21.4; 95% confidence interval [CI] 1.8-257.5) and alcoholism (aOR 6.5; 95% CI 1.3-32.8) were important predictive factors for spinal sepsis(18a).
C. Complications and diseases associated to Sepsis
C.1. Complcations
1. Impaired wound healing
Sepsis is one of the main causes for morbidity and mortality in hospitalized patients. Moreover, sepsis associated complications involving impaired wound healing are common(19).
2. Damage to Peripheral nerves and skeletal muscles
Among the critical illness myopathies, three main types have been identified: a non-necrotizing "cachectic" myopathy (critical illness myopathy in the strict sense), a myopathy with selective loss of myosin filaments ("thick filament myopathy") and an acute necrotizing myopathy of intensive care. Clinical manifestations of both critical illness myopathies and CIP include delayed weaning from the respirator, muscle weakness, and prolonging of the mobilization phase, according to the study by Ruprecht-Karls University, Heidelberg(20).
3. Organs failure
Bacterial translocation is the invasion of indigenous intestinal bacteria through the gut mucosa to normally sterile tissues and the internal organs. Bacterial translocation may be a normal phenomenon occurring on frequent basis in healthy individuals without any deleterious consequences. But when the immune system is challenged extensively, it breaks down and results in septic complications at different sites away from the main focus. The factors released from the gut and carried in the mesenteric lymphatics but not in the portal blood are enough to cause multi-organ failure, according to Postgraduate Institute of Medical Education and Research(21).
4. Morbidity and mortality
Acute kidney injury (AKI) is a common and often catastrophic complication in hospitalized patients; however, the impact of AKI in surgical sepsis remains unknown. We used Risk, Injury, Failure, Loss, End stage (RIFLE) consensus criteria to define the incidence of AKI in surgical sepsis and characterize the impact of AKI on patient morbidity and mortality(22). Other study indicated that in patients with sepsis who are admitted to an ICU, cardiac troponin T elevations are independently associated with in-hospital and short-term mortality but not long-term mortality(23).
C.2. Diseases associated to Sepsis
1. Staphylococcal infections
Preterm infants are especially susceptible to late-onset sepsis that is often due to Gram-positive bacterial infections resulting in substantial morbidity and mortality(24).
2. Elevated central venous pressure
Elevated central venous pressure is associated with impairment of microcirculatory blood flow in sepsis(25).
3. Neonatal cellulitis
there is a report of a case of late onset neonatal invasive group A streptococcal disease characterized with rapidly progressing cellulitis and development of sepsis(26).
4. Methicillin-resistant Staphylococcus aureus
There is a report of the spectrum of community-acquired S. aureus infections and to compare the patients infected with methicillin-susceptible or methicillin-resistant strains among patients aged <20 years. Overall, 90 cases of community-acquired S. aureus were detected in an 11-year period(27).
5. Bladder infection
Bladder bacteria is common but unique cause for sepsis(28).
6. Urinary tract infection
In the study to evaluate the effectiveness of Lactobacillus GG supplementation in reducing the incidence of urinary tract infections (UTIs), bacterial sepsis and necrotizing enterocolitis (NEC) in preterm infants, found that seven days of Lactobacillus GG supplementation starting with the first feed is not effective in reducing the incidence of UTIs, NEC and sepsis in preterm infants. Further studies are required to confirm our results in lower birthweight populations(29).
7. Venous thromboembolism (VTE) (deep venous thrombosis and pulmonary embolus)
According to the study b ythe UC Davis School of Medicine, there was increased risk of AbVTE early (<90 days; hazard ratio [HR] 5.4 [confidence interval (CI), 2.3-12.5]), but not late (≥90 days; HR 1.5 [CI, 0.9-2.6]) after splenectomy. There was increased risk of VTE both early (HR 5.2 [CI, 3.2-8.5]) and late (HR 2.7 [CI, 1.9-3.8]) after splenectomy. The cumulative incidence of sepsis was 11.1% among the ITP patients who underwent splenectomy and 10.1% among the patients who did not. Splenectomy was associated with a higher adjusted risk of sepsis, both early (HR 3.3 [CI, 2.4-4.6]) and late (HR 1.6 or 3.1, depending on comorbidities). ITP patients post splenectomy are at increased risk for AbVTE, VTE, and sepsis(30).
8. Hydroureteronephrosis
Hydroureteronephrosis without vesicoureteral reflux or lower-urinary-tract obstruction is uncommon in infants. There has been considerable interest in and controversy over the cause and management of this entity. We have cared for three neonates with severe hydroureteronephrosis after acute urinary tract infections, who were treated without operation, according to Pais VM, and Retik AB(31).
9. Osteomyelitis
Sepsis and osteomyelitis about the ankle joint present a challenging clinical problem. Osteomyelitis usually follows open fracture of the distal tibia, often with a pilon fracture component. Treatment of subsequent osteomyelitis and sepsis, including the authors' experiences, is discussed. Septic ankle arthritis can occur hematogenously. In some patients, the optimal treatment for concomitant osteomyelitis and sepsis is a below knee amputation(32).
10. Necrotizing fasciitis
There is a report of a case of necrotizing fasciitis and sepsis caused by Aeromonas hydrophila after crush injury of the lower extremity(33).
11. Phlebitis
There is a report of a case of Septic pulmonary emboli secondary to internal jugular vein phlebitis (postanginal sepsis) caused by Eikenella corrodens(34).
12. Lymphedema
There is a report of a patient with congenital penoscrotal lymphedema complicated by cellulitis, lymphangitis, and severe sepsis associated with a streptococcal infection. This case represents the importance of obtaining a detailed clinical history and physical findings(35).
13. Vancomycin-Resistant Enterococci (VRE)
The prevalence of the VRE that caused bacteraemia increased from 2003 to 2010. This increase might be attributed to the clonal spread of VREfm belonging to ST18 and ST414. The all-cause 14 day mortality rate was lower in patients with bacteraemia due to VREfm isolates that belonged to ST414(36).
D. Misdiagnosis and diagnosis
D.1. Misdiagosis
1. Delayed diagnosis
There is a report of encountered a case where the diagnosis of malarial infection in a woman with acute puerperal sepsis was significantly delayed(37). Others report a case of Necrotizing fasciitis (NF), a rare polymicrobial infection that can be life-threatening. It is a rapidly progressive inflammatory process affecting the deep fascia, with secondary necrosis of the subcutaneous tissue. Misdiagnosis and delayed treatment can result in death from sepsis, mediastinitis, carotid artery erosion, jugular vein thrombophlebitis, or aspiration pneumonia(38).
2. Delirium
There is a report of three cases of a 65-year-old woman, admitted for malnutrition, has significant mood-related symptoms that resemble depression, a 50-year-old male, admitted with an abscess, necrotizing fasciitis and sepsis, appears to be suicidal and 61-year-old male, admitted with pneumonia, has auditory hallucinations. All three patients turned out to have a delirium(39).
3. Fatal sepsis
There is a report of a case of fatal sepsis caused by infection with Klebsiella variicola, which is an isolate genetically related to Klebsiella pneumoniae. The patient's condition was incorrectly diagnosed as common sepsis caused by K. pneumoniae, which was identified using an automated identification system, but next-generation sequencing and the non-fermentation of adonitol finally identified the cause of sepsis as K. variicola(40).
4. Shigella sonnei
There is a report of a case of sepsis, caused by a commensal inactive Escherichia coli, which had been repeatedly misidentified as Shigella sonnei by VITEK 2 compact(41).
D.2. Diagnosis
According to the study by the Mustafa Kemal University, in cases of severe sepsis and septic shock, lactate clearance early in the hospital course may indicate a resolution of global tissue hypoxia and is associated with decreased mortality rate. Patients with higher lactate clearance after 6 hrs of emergency department intervention have improved outcome compared with those with lower lactate clearance(42).
If you are experience certain symptoms of the above and your doctor suspects that you have developed Sepsis, after recording the past and present history and completing a physical exam, the tests which your doctor orders may include
1. The table of sepsis diagnostic criteria
Table 1. Diagnostic criteria for sepsis
[Levy M, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003;31:1250-6]
| Infection, documented or suspected*, and some of the following: |
| General variables |
Fever (> 38.3 °C) |
| Inflammatory variables |
Leukocytosis (WBC count > 12,000/uL |
| Hemodynamic variables |
Arterial hypotension |
| Organ dysfunction variables |
Arterial hypoxemia |
| Tissue perfusion variables |
Elevated blood lactate |
2. The Laboratory tests
The aim is the test is to identify the infectious agent causing the infections. According to the study by the Stanford University School of Medicine, definitive diagnosis depends on cultures of blood or other normally sterile body fluids. Abnormal hematological counts, acute-phase reactants, and inflammatory cytokines are neither sensitive nor specific, especially at the onset of illness. Combinations of measurements improve diagnostic test performance, but the optimal selection of analytes has not been determined. The best-established use of these laboratory tests is for retrospective determination that an infant was not infected, based on failure to mount an acute-phase response over the following 24 to 48 hours(43).
E. Preventions
E.1. Diet to prevent sepsic
1. Onions
The onion is a plants in the genus Allium, belongs to the family Alliaceae, a close relation of garlic. It It is often called the "king of vegetables" because of its pungent taste and found in a large number of recipes and preparations spanning almost the totality of the world's cultures. Depending on the variety, an onion can be sharp, spicy, tangy, pungent, mild or sweet. Since it contains high amount of antioxidants, onion enhances the immune system in fighting against the forming of free radicals and foreign invasion, thus eeducing the symptoms of inflammatory conditions such as arthritis and gout and infection caused by bacteria, including E.coli and salmonella,etc., according to the study of Antibacterial and antioxidant activities of quercetin oxidation products from yellow onion (Allium cepa) skin." by Ramos FA, Takaishi Y, Shirotori M, Kawaguchi Y, Tsuchiya K, Shibata H, Higuti T, Tadokoro T, Takeuchi M., posted in PubMed(45).
2. Blueberries
Blueberry is a flower plant, belong to the family Eriaceae and native to Northern America. It can grows from 10 cm to 4 meters tall.
a. Antioxidant Capacity
In the investigation of Blueberry and blackberry wines commercially available in Illinois and theirs potential health benefits, found that fruit wines made from blueberries and blackberries may have potential health applications and therefore could contribute to the economy of the wine industry. Practical Application: The majority of wines are produced from grapes, but wine can also be produced from other fruits including blueberries and blackberries, which contain phenolic compounds that may contribute to human health, according to "Comparison of Chemical Composition and Antioxidant Capacity of Commercially Available Blueberry and Blackberry Wines in Illinois" by Johnson MH, Gonzalez de Mejia E.(46).
b. Inflammatory bowel diseases
In the study of blueberries and broccoli in mdr1a(-/-) mice (IBD mouse model) for theirs effect gastrointestinal tract, found that blueberry- and broccoli-supplemented diets increased colon crypt size and the number of goblet cells per crypt. Only the broccoli-supplemented diet significantly lowered colonic inflammation compared to mice fed the control diet, according to "Influence of dietary blueberry and broccoli on cecal microbiota activity and colon morphology in mdr1a(-/-) mice, a model of inflammatory bowel diseases" by Paturi G, Mandimika T, Butts CA, Zhu S, Roy NC, McNabb WC, Ansell J.(47).
3. Mushroom
Mushroom is a standard name of white button mushroom, the fleshy, spore-bearing fruiting body of a fungus produced above ground on soil or on its food source, It is a genus A. Muscaria and belong to the family Amanitaceae and has been cultivation in many cultures all over the world for foods and health benefits.
In the analyzing White button mushrooms (WBM) and its effect in immune response, found that WBM promote DC maturation and enhance their antigen-presenting function. This effect may have potential in enhancing both innate and T cell-mediated immunity leading to a more efficient surveillance and defense mechanism against microbial invasion and tumor development, according to "White button mushroom enhances maturation of bone marrow-derived dendritic cells and their antigen presenting function in mice" by Ren Z, Guo Z, Meydani SN, Wu D.(48).
4. Green Tea
a. Immune system
In the investigation of the immunomodulatory effects of decaffeinated green tea extract in rain bow of the study of "Immunomodulatory effects of decaffeinated green tea (Camellia sinensis) on the immune system of rainbow trout (Oncorhynchus mykiss)" by Sheikhzadeh N, Nofouzi K, Delazar A, Oushani AK(49), researchers found that showed that decaffeinated green tea in lower doses of administration could be optimum to enhance the immunity of rainbow trout.
b. Antimicrobial activities
a. In the investigation of Antimicrobial activities of green of the study of "Antimicrobial activities of tea catechins and theaflavins and tea extracts against Bacillus cereus" by Friedman M, Henika PR, Levin CE, Mandrell RE, Kozukue N.(50), researchers found that flavonoids in green tea has exerted its ability in protective effects against Bacillus cereus.
2. Phytochemicals and antioxidants to prevent sepsis
1. Vitamin A and Immunity as antioxidants
Vitamin A occurs in the form retinol and is best known for its function in maintaining the health of cell membrane, hair, skin, bone, teeth and eyes. It also plays an important role as an antioxidant as it scavenges free radicals in the lining of the mouth and lungs; prevents its depletion in fighting the increased free radicals activity by radiation; boosts immune system in controlling of free radicals; prevents oxidation of LDL and enhances the productions of insulin pancreas(51).
2. High dose of vitamin C and Immune system
In the first comparative analysis of the ex vivo and in vitro molecular and cellular mechanisms of action of IFN-α and high-dose AA in HAM/TSP, found that in comparison to IFN-α, high-dose AA treatment has superior ex vivo and in vitro cell death-inducing, antiproliferative and immunomodulatory anti-HTLV-1 effects. Differential pathway activation by both drugs opens up avenues for targeted treatment in specific patient subsets(52).
3. Vitamin E and Immunity
Vitamin E is the most important chain-breaking, lipid-soluble antioxidant present in body tissues of all cells and is considered the first line of defense against lipid peroxidation and it is important for normal function of the immune cells. However, vitamin E deficiency is rare in well-nourished healthy subjects and is not a problem, even among people living on relatively poor diets, both T- and B-cell functions are impaired by vitamin E deficiency. While immune cells are particularly enriched in vitamin E because of their high polyunsaturated fatty acid content, this point puts them at especially high risk for oxidative damage, according to the study by Dr. Pekmezci D. at the University of Ondokuz Mayıs(53).
4. Allyl sulfides and Immune system
According to the article of "GARLICTHE BOUNTIFUL BULB" by Carmia Borek, Ph.D. posted in Life extension magazine, the author indicated that human studies confirm immune stimulation by garlic. Subjects receiving aged garlic extract at 1800 mg a day for three weeks showed a 155.5% increase in natural killer immune cell activity that kills invaders and cancer cells. Other subjects receiving large amounts of fresh garlic of 35g a day, equivalent to 10 cloves, showed an increase of 139.9%. In six weeks, patients with AIDS receiving aged garlic extract showed an enhancement of natural killer cells from a seriously low level to a normal level(54).
5. Allicin is phytochemical containing sulfur in the class of organosulfur compound, found abundantly in onion and garlic.
Antibacterial activities
In the comparison of those of allicin and several clinically useful antibiotics using two representative bacteria commonly found in the human environment, Gram-positive S. aureus and Gram-negative Escherichia coli, indicated that The garlic extract had more potent anti-staphylococcal activity than an equal amount of allicin. In terms of antibiotic potency against Gram-positive and Gram-negative bacteria, authentic allicin had roughly 1-2% of the potency of streptomycin (vs. S. aureus), 8% of that of vancomycin (vs. S. aureus), and only 0.2% of that of colistin (vs. E. coli), according to "Antibacterial potential of garlic-derived allicin and its cancellation by sulfhydryl compounds" by Fujisawa H, Watanabe K, Suma K, Origuchi K, Matsufuji H, Seki T, Ariga T.(54).
6. Cinnamon
a. Immunomodulatory effect
In administration of popular herb used in traditional medicine to treat various disorders such as chronic gastric symptoms, arthritis, and the common cold and its immunomodulatory effect found that observations provided evidence that CWE was able to down-regulate IFN-γ expression in activated T cells without altering IL-2 production, involving inhibition of p38, JNK, ERK1/2, and STAT4, according to the study of "Immunomodulatory effect of water extract of cinnamon on anti-CD3-induced cytokine responses and p38, JNK, ERK1/2, and STAT4 activation" by Lee BJ, Kim YJ, Cho DH, Sohn NW, Kang H.(55)
b. Antimicrobial Activities
In the observation of three natural essential oils (i.e., clove bud oil, cinnamon oil, and star anise oil) and their antimicrobal effects found that the cinnamon oil-chitosan film had also better antimicrobial activity than the clove bud oil-chitosan film. The results also showed that the compatibility of cinnamon oil with chitosan in film formation was better than that of the clove bud oil with chitosan, according to the study of "Synergistic Antimicrobial Activities of Natural Essential Oils with Chitosan Films" by Wang L, Liu F, Jiang Y, Chai Z, Li P, Cheng Y, Jing H, Leng X.(56)
c. Anti-inflammatory activity
In the investigation of Myristicin (1-allyl-5-methoxy-3,4-methylenedioxybenzene) is an active aromatic compound found in nutmeg (the seed of Myristica fragrans), carrot, basil,cinnamon, and parsley and it anti-inflammatory effects found that Myristicin significantly inhibited the production of calcium, nitric oxide (NO),interleukin (IL)-6, IL-10, interferon inducible protein-10, monocyte chemotactic protein(MCP)-1, MCP-3, granulocyte-macrophage colony-stimulating factor, macrophage inflammatory protein (MIP)-1α, MIP-1β, and leukemia inhibitory factor in dsRNA[polyinosinic-polycytidylic acid]-induced RAW 264.7 cells (P < 0.05), according to the study of "Anti-inflammatory effect of myristicin on RAW 264.7 macrophages stimulated with polyinosinic-polycytidylic acid" by Lee JY, Park W.(57)
F. Treatments
E.1. Treatments in conventional medicine perspective
1. Antibiotics
Most case of sepsis are treated with combination of two or three antibiotics given at the same time.
High doses of vancomycin were administered in order to rescue patients from septic shock. Plasma drug concentration dropped while clinical condition of patients worsened. Conversely, drug levels increased spontaneously once the infection was reverted. The theoretical model provided greater insight into pharmacokinetic features related with the use of vancomycin in septic patients(58). Other study indicated that patients with sepsis do not seem to have the same level of impairment of tissue distribution as described for patients with septic shock. A 25% lower dose of piperacillin administered by continuous infusion seems to maintain higher trough concentrations compared with standard bolus dosing. It is likely that the clinical advantages of continuous infusion are most likely to be evident when treating pathogens with high minimum inhibitory concentration, although without therapeutic drug monitoring and subsequent dose adjustment, infusions may never achieve target concentrations of organisms with very high minimum inhibitory concentrations in a small number of patients(59).
2. IV Fluids
In the study to determine the clinical and pharmacokinetic differences between continuous and intermittent dosing in patients with severe sepsis, found that continuous administration of beta-lactam antibiotics achieved higher plasma antibiotic concentrations than intermittent administration with improvement in clinical cure. This study provides a strong rationale for further multicenter trials with sufficient power to identify differences in patient-centered endpoints(60). Other study suggested that routine use of prolonged infusion of time-dependent antibiotics for the empiric treatment of gram-negative bacterial infections offers no advantage over intermittent infusion antibiotic therapy with regard to treatment success, mortality, or hospital length of stay. These results were confirmed after controlling for potential confounders in a multivariate analysis(61).
E.2. Treatments in herbal medicine perspective
1. Taraxacum coreanum
Taraxacum coreanum Nakaiis a dandelion native to Korea and is widely consumed as an edible and medicinal herb. Treatment of primary macrophages with Taraxacum coreanum chloroform fraction(TCC) in vitro significantly inhibited all of the inflammatory parameters measured, including LPS-induced NO and PGE2 production, iNOS and COX-2 expression, IκBα degradation, IKK phosphorylation, and MAPK and STAT1 activation. In a mouse model of LPS-induced septic shock, TCC inhibited the production of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, and increased survival by 83%.Standard compounds (gallic acid, syringic acid) of Taraxacum coreanum were qualified by HPLC analysis, according to Kyung Hee University(62).
2. Chamaecyparis obtusa
β-thujaplicin, an active constituent from Chamaecyparis obtusa, has been shown to have acaricidal and antimicrobial effects. According to the study by the Chia-Nan University of Pharmacy and Science, the potential of β-thujaplicin in treatment of inflammation and sepsis. These effects occur through an efficient blockage of TNF-alpha and iNOS production. β-thujaplicin efficacy is comparable to that of indomethacin thus it can be a substitution but bear less depletion of PGE2, making this compound very promising in clinical applications(63).
3. Angelica sinensis
A low-molecular-weight (<10 kDa) fraction of A. sinensis extract significantly attenuated endotoxin-induced HMGB1 release in part through interfering with its cytoplasmic translocation in macrophage cultures. Prophylactic administration of an aqueous extract of A. sinensis significantly attenuated systemic HMGB1 accumulation in vivo, and conferred a dose-dependent protection against lethal endotoxemia. Furthermore, delayed administration of A. sinensis extract beginning 24 h after CLP attenuated systemic HMGB1 accumulation, and significantly rescued mice from lethal sepsis. Taken together, these data suggest that A. sinensis contains water-soluble components that exert protective effects against lethal endotoxemia and experimental sepsis in part by attenuating systemic accumulation of a late proinflammatory cytokine, HMGB1, according to the New York University School of Medicine(64).
4. Green tea
Intraperitoneal administration of EGCG protected mice against lethal endotoxemia, and rescued mice from lethal sepsis even when the first dose was given 24 hours after cecal ligation and puncture. The therapeutic effects were partly attributable to: 1) attenuation of systemic accumulation of proinflammatory mediator (e.g., HMGB1) and surrogate marker (e.g., IL-6 and KC) of lethal sepsis; and 2) suppression of HMGB1-mediated inflammatory responses by preventing clustering of exogenous HMGB1 on macrophage cell surface, according to the study by the North Shore University Hospital-New York University School of Medicine(65).
E.3. Treatments in traditional Chinese medicine perspective
1. Cortex lycii Cortex lycii with both highest affinities was selected out from one hundred and fourteen traditional Chinese herbs. In subsequent experiments, chromatography was utilized and coupled with the biosensor to purify fractions with a higher affinity for LPS and CpG DNA. In line with affinity assay, these fractions were shown to neutralize LPS and CpG DNA and inhibit their activity in vitro and in vivo. Lastly, the contributing monomer Kukoamine B (KB) was purified. KB neutralized LPS and CpG DNA in vitro. It inhibited TLR4, TLR9 and MyD88 mRNA expressions up-regulated by LPS and CpG DNA, and also attenuated the LPS and CpG DNA elicited nuclear translocation of NF-κB p65 protein in RAW264.7 cells. It also protected mice from lethal challenge of heat-killed E. coli, a mixture of LPS and CpG DNA(66).
2. Magnolia officinalis
Magnolol is a compound extracted from the Chinese medicinal herb Magnolia officinalis. In the study to evaluate the effects of magnolol on sepsis induced by intravenous (i.v.) administration of lipopolysaccharide (LPS; 10 mg/kg) in anaesthetized Wistar rats with Magnolol (4 microg/kg, i.v.) was administered at 30 min after LPS injection, found that post-treatment with magnolol significantly attenuated the deleterious haemodynamic changes (e.g., hypotension and bradycardia) caused by LPS. Meanwhile, magnolol significantly inhibited the elevation of plasma levels of tumor necrosis factor alpha, glutamate-oxaloacetate transaminase, glutamate-pyruvate transaminase and blood urine nitrogen caused by LPS. The induction of inducible nitrous oxide (NO) synthase and the overproduction of NO and superoxide anions by LPS were also significantly reduced by post-treatment with magnolol. Moreover, the plasma level of the thrombin-antithrombin complex following administration of LPS was also reduced by post-treatment with magnolol(67).
3. Terminaliachebula Retz
Terminaliachebula Retz was found to possess the highest capability of binding lipid A. With CER (cation-exchange resin) and HPLC, the extracted from Terminaliachebula Retz, and named them TCR1, TCR2 and TCR3 respectively was found that the TCR3 was the most capable candidate to bind lipid A. We also studied the biological activities of TCR3 against sepsis in vitro and in vivo. in vitro, TCR3 could significantly inhibit LPS (lipopolysaccharide)-induced LAL (Limulus amoebocyte lysate)) from agglutination and decrease TNFalpha (tumour necrosis factor alpha) release from RAW264.7 cells induced by LPS in a dose-dependent manner. in vivo, TCR3 could significantly protect mice against a lethal challenge with LPS and heat-killed Escherichia coli 35218 in a dose-dependent manner(68).
4. Scutellaria baicalensis Georgi (Huang Qin)
2',5,6',7-tetrahydroxyflavanonol (THF) from S. baicalensis Georgi under the direction of neutralization of LPS and reducing proinflammatory cytokines. In vitro, THF directly bound to LPS and neutralized its activity. THF not only down-regulated TNF-alpha mRNA expression but also decreased TNF-alpha and IL-6 release from RAW264.7 cells induced by LPS in a dose-dependent manner. THF-mediated inhibition on proinflammatory cytokine release is probably associated with downregulation of LPS-induced TLR4 mRNA augmentation. In vivo, THF could significantly protect mice against a lethal challenge with heat-killed E. coli 35218 (E. coli 35218) in a dose-dependent manner, and decreased the plasma LPS level in endotoxemia mice, according to Third Military Medical University(69).
Sources
(a) http://en.wikipedia.org/wiki/Sepsis
(b) http://www.mayoclinic.com/health/sepsis/DS01004
(c) http://www.ncbi.nlm.nih.gov/pubmed/24082613
(1) http://www.ncbi.nlm.nih.gov/pubmed/24040479
(2) http://www.ncbi.nlm.nih.gov/pubmed/20813272
(3) http://www.ncbi.nlm.nih.gov/pubmed/23635850
(4) http://www.ncbi.nlm.nih.gov/pubmed/23915595
(5) http://www.ncbi.nlm.nih.gov/pubmed/19579754
(6) http://www.ncbi.nlm.nih.gov/pubmed/24069571
(7) http://www.ncbi.nlm.nih.gov/pubmed/24037335
(8) http://www.ncbi.nlm.nih.gov/pubmed/23133376
(9) http://www.ncbi.nlm.nih.gov/pubmed/20149587
(10) http://www.ncbi.nlm.nih.gov/pubmed/23091606
(11) http://www.ncbi.nlm.nih.gov/pubmed/22905169
(12) http://www.ncbi.nlm.nih.gov/pubmed/24019843
(13) http://www.ncbi.nlm.nih.gov/pubmed/24067565
(14) http://www.ncbi.nlm.nih.gov/pubmed/19579754
(15) http://www.ncbi.nlm.nih.gov/pubmed/22251396
(16) http://www.ncbi.nlm.nih.gov/pubmed/23153889
(17) http://www.ncbi.nlm.nih.gov/pubmed/20698966
(18) http://www.ncbi.nlm.nih.gov/pubmed/4931311
(18a) http://www.ncbi.nlm.nih.gov/pubmed/19632847
(19) http://www.ncbi.nlm.nih.gov/pubmed/24086305
(20) http://www.ncbi.nlm.nih.gov/pubmed/11757954
(21) http://www.ncbi.nlm.nih.gov/pubmed/24064638
(22) http://www.ncbi.nlm.nih.gov/pubmed/24089113
(23) http://www.ncbi.nlm.nih.gov/pubmed/24083646
(24) http://www.ncbi.nlm.nih.gov/pubmed/23935651
(25) http://www.ncbi.nlm.nih.gov/pubmed/23919272
(26) http://www.ncbi.nlm.nih.gov/pubmed/20807361
(27) http://www.ncbi.nlm.nih.gov/pubmed/24055391
(28) http://www.ncbi.nlm.nih.gov/pubmed/5564785
(29) http://www.ncbi.nlm.nih.gov/pubmed/12169832
(30) http://www.ncbi.nlm.nih.gov/pubmed/23637127
(31) http://www.ncbi.nlm.nih.gov/pubmed/1089891
(32) http://www.ncbi.nlm.nih.gov/pubmed/11232476
(33) http://www.ncbi.nlm.nih.gov/pubmed/18687029
(34) http://www.ncbi.nlm.nih.gov/pubmed/6383158
(35) http://www.ncbi.nlm.nih.gov/pubmed/11138888
(36) http://www.ncbi.nlm.nih.gov/pubmed/22618861
(37) http://www.ncbi.nlm.nih.gov/pubmed/24032986
(38) http://www.ncbi.nlm.nih.gov/pubmed/23790808
(39) http://www.ncbi.nlm.nih.gov/pubmed/23693007
(40) http://www.ncbi.nlm.nih.gov/pubmed/23449877
(41) http://www.ncbi.nlm.nih.gov/pubmed/22029193
(42) http://www.ncbi.nlm.nih.gov/pubmed/15286537
(43) http://www.ncbi.nlm.nih.gov/pubmed/20569816
(44) http://www.biomerieux-diagnostics.com/servlet/srt/bio/clinical-diagnostics/dynPage?open=CNL_HCP_INF_SEP&doc=CNL_HCP_INF_SEP_G_CHP_TXT_1&pubparams.sform=2&lang=en
(45) http://www.ncbi.nlm.nih.gov/pubmed/19127724
(46) http://www.ncbi.nlm.nih.gov/pubmed/22182198
(47) http://www.ncbi.nlm.nih.gov/pubmed/22113065
(48) http://www.ncbi.nlm.nih.gov/pubmed/18287364
(49) http://www.ncbi.nlm.nih.gov/pubmed/21985858
(50) http://www.ncbi.nlm.nih.gov/pubmed/16496576
(51) http://medicaladvisorjournals.blogspot.ca/2012/01/antioxidants-and-common-free-radical.html
(52) http://www.ncbi.nlm.nih.gov/pubmed/22848768
(53) http://www.ncbi.nlm.nih.gov/pubmed/21419272
(54) http://www.ncbi.nlm.nih.gov/pubmed/19734685
(55) http://www.ncbi.nlm.nih.gov/pubmed/22053946
(56) http://www.ncbi.nlm.nih.gov/pubmed/22034912
(57) http://www.ncbi.nlm.nih.gov/pubmed/21991618
(58) http://www.ncbi.nlm.nih.gov/pubmed/18397685.
(59) http://www.ncbi.nlm.nih.gov/pubmed/19237898
(60) http://www.ncbi.nlm.nih.gov/pubmed/23074313
(61) http://www.ncbi.nlm.nih.gov/pubmed/23341160
(62) http://www.ncbi.nlm.nih.gov/pubmed/23261487
(63) http://www.ncbi.nlm.nih.gov/pubmed/22507316
(64) http://www.ncbi.nlm.nih.gov/pubmed/16424112
(65) http://www.ncbi.nlm.nih.gov/pubmed/17987129
(66) http://www.ncbi.nlm.nih.gov/pubmed/21073991
(67) http://www.ncbi.nlm.nih.gov/pubmed/20519137
(68) http://www.ncbi.nlm.nih.gov/pubmed/19203350
(69) http://www.ncbi.nlm.nih.gov/pubmed/18755299
Sources
(a) http://www.ncbi.nlm.nih.gov/pubmed/9086580
(b) http://www.merckmanuals.com/professional/endocrine_and_metabolic_disorders/thyroid_disorders/euthyroid_sick_syndrome.html
(c) http://en.wikipedia.org/wiki/Euthyroid_sick_syndrome
(d) http://www.ncbi.nlm.nih.gov/pubmed/8028742
(1) http://clinicalcases.org/2004/05/sick-euthyroid-syndrome-in-patient-with.html
Malignancy
Malignancy is defined as a medical condition of the the cells of the body have become cancerous, with the tendency to spread to other part of the body. For most comon types of cancer, please visit
*What is Cancer
Euthyroid sick syndrome and cancers
1. Euthyroid sick syndrome and Skin cancer
2. Euthyroid sick syndrome and bone or soft tissue cancers
According to the study by the University Hospital, Rotterdam, Cytokines have been implicated in the pathogenesis of the euthyroid sick syndrome. Isolated limb perfusion (ILP) with recombinant human tumor necrosis factor alpha (rTNF) and melphalan in patients with melanoma or sarcoma is accompanied by high systemic(1) http://www.ncbi.nlm.nih.gov/pubmed/10094108
*Bladder Cancer
*Bladder Cancer In Traditional Chinese Medicine Perspective
*Bone Cancer (Osteosarcoma and Other Types)
*Bone Cancer In Traditional Chinese Perspective
Brain and Spinal Cord Cancer
Cancer of Esophagus/Esophageal Cancer
*Cervical Cancer
Bowel Cancer (Colon and rectum)
*Breast Cancer
*Cancer with unknown primary site (CUP)
*Choriocarcinoma and Hydatidiform Mole(Tumors and Placenta)
*Cancer of Endometrium ( Womb)
*Esophagueal cancer
*Hodgkin's diseases
*Kaposi's Sarcoma
*Kidney Cancer (Renal cell Carcinoma)
*Larynx (Voice Box) Cancer/Laryngeal Cancer
Pharynx (Throat) Cancer
Leukemias
*a. Lymphoblastic leukemia- Chronic lymphoblastic leukemia (CLL)
b. Myelogenous leukemia - Chronic myelogenous leukemia (CML)
c. Lymphoblastic leukemia - Acute lymphoblastic leukemia (ALL)
d. Myelogenous leukemia - Acute myelogenous leukemia (AML)
Liver Cancer (Hepatocellular carcinoma)
*Lung cancer
(Non-small-cell and small cell lung cancer)
*Lymphoma (No-Hodgkin's Lymphoma(The Indolent Lymphomas and The high grade Lymphomas)
*Melanoma skin cancer ( Malignant Melanoma)
*Mouth ( Oral ) cancer
*Myeloma (Multiple Myenoma)
Ovary
Ovarian Cancer - Sex cord stromal ovarian cancer
*Ovarian Cancer - Epithelial ovarian Cancer
Ovarian Cancer - Germ Cell Ovarian Cancer
*Pancreatic Cancer (Exocrine Cancers)
*Prostate Cancer
Others
*Sarcomas of the soft tissues
Skin cancers (excluding Melanoma)
*Stomach cancer
*Testicular cancer
*Thyroid
Small Lung cancer
In the study to determine the frequency of sick euthyroid syndrome (SES) among patients diagnosed as non-small cell lung cancer (NSCLC) and its association with the stage of the disease of enrolled 80 consecutive patients with newly diagnosed NSCLC, indicated that of out of 80 patients, sick euthyroid syndrome (SES) were identified in 28 (35%). SES was more frequent among stage III (26%) and stage IV (62%) cases. The body mass index (BMI), KI and serum albumin level were detected to be significantly low in cases with SES when compared to cases without SES. SES was found to be negatively correlated with BMI, KI and serum albumin level, and it was positively correlated with disease stage. SES was frequently seen in cases with NSCLC. SES can be used as a predictor of poor prognosis. http://www.ncbi.nlm.nih.gov/pubmed/18701976http://www.ncbi.nlm.nih.gov/pubmed/18701976
Thyroid cancer
and Multiple myeloma
Heart failure
Heart failure (HF), or congestive heart failure, is defined as a condition as a result of damaged or weakened by the diseases of the heart such as heart attacks. HF occurs when the heart is unable to provide sufficient pump action to maintain blood flow to meet the needs of the body, especially during increased activity or under stress(a)(b).
A. Symptoms
1. Depression
Depression is common in patients with cardiac disease, especially in patients with heart failure, and is associated with increased risk of adverse health outcomes(1).
2. Edema
There is a report of a case of 71-year old lady with a dual chamber demand pacemaker, who developed acute pulmonary edema due to an acute left ventricular (LV) dysfunction and worsening in mitral valve regurgitation after atrioventricular nodal ablation for uncontrolled atrial fibrillation(2).
3. Hyponatremia
In the review analyses the mechanisms relating heart failure and hyponatremia, indicated that patients with heart failure often develop hyponatremia owing to the activation of many neurohormonal systems leading to decrease of sodium levels. A large number of clinical studies have associated hyponatremia with increased morbidity and mortality in patients hospitalized for heart failure or outpatients with chronic heart failure(3).
4. Shortness of air
according to the study by the McGill University, certain health-related indices and environmental conditions affect self-reported health and shortness of breath in CHF patients, although larger studies are needed to confirm these findings(4).
5. Fatigue
Fatigue is a prominent and poorly understood symptom of heart failure with reduced ejection fraction (HFrEF)(5).
6. Irregular and Rapid heart beat
Patients with congestive heart failure had significantly higher beat-to-beat QRS amplitude variability compared to controls in resting supine posture. This may partly be due to myocardial disease or irregular respiration in this patient group(6).
7. Reduced ability to exercise
The minute ventilation-carbon dioxide production relationship VE/VCO2 slope, as an index of ventilatory response to exercise, is an excellent prognostic parameter and improves the risk stratification of CHF patients. It is easier to obtain than parameters of maximal exercise capacity and is of equivalent prognostic importance than peak VO2(7).
8. Cough and night sweats and
Cough was more frequent in class I or II patients (28%) than in class III (4.1%, p<0.01) and class IV (0%, p<0.01) patients(8). Other study reported a case of 66-year-old woman with a history of myocardial infarction 2 months prior presented to our respiratory department with several days of dry cough and night sweats. Chest X-ray and thoracic CT showed ground glass opacities or consolidation spreading from the hilar area to the peripheral area, suggesting central redistribution. Although neither rales nor abnormal heart sounds were noted, she was tentatively diagnosed with congestive heart failure based on those radiological findings(9).
9. Cardiac asthma
Cardiac asthma has been defined as wheezing, coughing and orthopnea due to congestive heart failureThe incidence of enalapril-induced cough was evaluated in 199 patients with congestive heart failure(10).
10. Abdominal complaints
Abdominal complaints are a common component of the presenting symptom complex of CHF in pediatric dilated cardiomyopathy in all age groups. In adolescents, abdominal complaints occur more frequently than respiratory complaints and often in the absence of any other symptoms. Unlike CHF in adults, chest pain, arrhythmia, or cardiac arrest occurs rarely at presentation in pediatric patients. Recognition of the different presenting symptoms of heart failure in children by primary providers is crucial to ensuring prompt diagnosis and timely initiation of therapy(11).
11. Constitutional symptoms
Constitutional symptoms such as nausea, lack of appetite, and fatigue are also common. There are several compensatory mechanisms that occur as the failing heart attempts to maintain adequate function(12).
12. Cerebral hypoperfusion
Cerebral hypoperfusion such as dizziness, hearing difficulties, and vision problems including blurring, dimming, or a total “blackout." Cerebral hypoperfusion is common in heart failure (HF) and believed to underlie poor neurocognitive outcomes in this population. Up to 42% of HF patients also exhibit depressive symptomatology that may stem from reduced cerebral blood flow, according to the study by the Kent State University(13).
13. Elevated blood pressure
It is well established that elevated blood pressure constitutes a major risk factor for coronary heart disease, arrythmias, heart failure, cerebrovascular disease, peripheral artery disease and renal failure(14).
B. Causes and Risk Factors
B.1. Causes
Heart failure (HF), or congestive heart failure, is caused by damaged or weakened by the diseases of the heart such as heart attacks.
1. Mitochondrial DNA
Heart failure is a leading cause of morbidity and mortality in industrialized countries. Although infection with microorganisms is not involved in the development of heart failure in most cases, inflammation has been implicated in the pathogenesis of heart failure, according to the study by the Osaka University Graduate School of Medicine(15).
2.
B.2. Risk Factors
C. Complications and Diseases associated to heart failure
C.1. Complications
C.2. Diseases associated to Postoperative hypothyroidism
D. Misdiagnosis and Diagnosis
D.1. Misdiagnosis
D.2. Diagnosis
E. Prevention
F. Treatments
Anorexia nervosa
Sources
(a) http://www.heartandstroke.com/site/c.ikIQLcMWJtE/b.3484065/k.C530/Heart_disease__Heart_failure.htm
(b) http://en.wikipedia.org/wiki/Heart_failure
(1) http://www.ncbi.nlm.nih.gov/pubmed/22851113
(2) http://www.ncbi.nlm.nih.gov/pubmed/24109499
(3) http://www.ncbi.nlm.nih.gov/pubmed/24109495
(4) http://www.ncbi.nlm.nih.gov/pubmed/19131052
(5) http://www.ncbi.nlm.nih.gov/pubmed/22939040
(6) http://www.ncbi.nlm.nih.gov/pubmed/17137652
(7) http://www.ncbi.nlm.nih.gov/pubmed/20657715
(8) http://www.ncbi.nlm.nih.gov/pubmed/18606471
(9) http://www.ncbi.nlm.nih.gov/pubmed/24001730
(10) http://www.ncbi.nlm.nih.gov/pubmed/23234454
(11) http://www.ncbi.nlm.nih.gov/pubmed/23380118
(12) http://www.ncbi.nlm.nih.gov/pubmed/22227365
(13) http://www.ncbi.nlm.nih.gov/pubmed/24022882
(14) http://www.ncbi.nlm.nih.gov/pubmed/24026758
(15) http://www.ncbi.nlm.nih.gov/pubmed/22535248
hypothermia, myocardial infarction, chronic renal failure, cirrhosis, and diabetic ketoacidosis and inflammatory bowel disease(c). inflammatory bowel disease, arthritis, sepsis, gastritis, asthma, atherosclerosis, such as osteoprotegerin (OPG), are associated with elevated mortality, especially from cardiovascular diseases(d) http://en.wikipedia.org/wiki/NF-%CE%BAB
http://www.jci.org/articles/view/7771
II.2. Hyperthyroidism
Hyperthyroidism is a condition in which the thyroid gland is over active and produces too much thyroid hormones.
A. Symptoms
B. Causes and Risk Factors
C. Complications and Diseases associated to Postoperative hypothyroidism
C.1. Complications
C.2. Diseases associated to Postoperative hypothyroidism
D. Misdiagnosis and Diagnosis
E. Prevention
F. Treatments
Thyroid stormGraves' disease
Toxic thyroid nodule
Toxic nodular struma (Plummer's disease)
Hashitoxicosis
III. Nodular abnormalities - Goitre
Endemic goitre
Diffuse goitre
Multinodular goitreLingual thyroid
Thyroglossal duct cyst
IV. Deficiencies
Cretinism is a condition of severely stunted physical and mental growth due to untreated congenital deficiency of thyroid hormones (congenital hypothyroidism) usually due to maternal hypothyroidism.
