Dietary Intervention as Alternative Cancer Treatments

Proponents of alternative diets claim that life prolongation through adherence to a particular diet is an achievable goal for cancer patients. However, a systematic review based on evidence found indicates that there is no diet regimen that has been conclusively proven to cure cancer or significantly prolong the life of cancer patients.

Gerson regimen — Hildenbrand et al (1995) analysis reported a six-fold increase in five-year survival rates of melanoma patients treated with the Gerson diet (a low sodium, high potassium, lactovegetarian diet that emphasizes fresh vegetables, fruit juices, and vitamin supplements), but the flawed methodology limits the reliability of this study. Therefore, no good evidence supports this approach.

Macrobiotic diets — Based on Carter et al (1993), scientific evidence of benefit from a macrobiotic diet (a high-complex carbohydrate, low fat vegetarian diet) in cancer patients is limited to two methodologically flawed retrospective studies; no controlled trials are available. In addition based on Downer et al (1994), one-third of cancer patients on a macrobiotic diet experience problems due to weight loss, the restrictive and unpalatable nature of the regimen, time spent preparing the food, and the expense and inaccessibility of some ingredients.

Kelley-Gonzalez regimen — The Kelley-Gonzalez regimen refers to a program of dietary restriction, intake of digestive aids (eg, pepsin and pancreatic enzymes), and a "detoxification" regimen that includes frequent coffee enemas. Gonzales et al (1999) studied 36 patients with unresectable or incompletely resected pancreatic cancer, only 11 were considered assessable for outcome for various reasons. The median survival of treated patients was 17 months, compared to a literature control of four to six months. A trial comparing this therapy with gemcitabine for pancreatic cancer was underway at Columbia University, but accrual issues forced a redesign of the study, which now compares outcome in patients who elect to receive the Gonzalez regimen with an externally matched group who receive standard gemcitabine-based combination chemotherapy.

Selected vegetables and herb mix — Selected vegetables and herb mix is a blended, boiled, and freeze-dried product containing ingredients with purported immune-stimulatory and anticancer properties: soybeans, mushrooms, mung beans, red dates, scallion, garlic, lentils, leek, hawthorn fruit, onion, ginseng, angelica, dandelion, senegal root, licorice, ginger, olives, sesame seeds, and parsley. In a matched-control study involving patients with stage III/IV non-small cell lung cancer (NSCLC), median survival duration among the 11 patients who ingested selected vegetables daily was three-fold longer than that of 13 patients who did not receive the supplement (15 versus 4 months). A similar suggestion of prolonged survival was noted in a second study of 18 patients with stage III/IV NSCLC who had either rejected or failed to respond to conventional therapies. The median survival was 33.5 months for the 12 patients who used selected vegetables for two months or longer, and at five years, 50 percent of the patients remained alive.

Lactose Intolerance

Intolerance to lactose-containing foods (primarily dairy products) is a common problem. The term lactose intolerance is applied to the development of characteristic symptoms after the ingestion of lactose: 

• abdominal pain, 
• bloating, 
• flatulence, 
• diarrhea, 
• and, particularly in adolescents, vomiting.

The causes of lactose malabsorption can be divided into : 

• primary lactase deficiency 
• and lactase deficiency induced by underlying intestinal disease.

The term lactose malabsorption is generally reserved for those patients with typical symptoms in whom the intestinal malabsorption of lactose has been confirmed by a test of absorption (eg, lactose absorption test) or malabsorption (lactose breath hydrogen test). 

The approach to patients with lactose malabsorption in the absence of a correctable underlying disease includes four general principles:

• Reduced dietary lactose intake.
• Substitution of alternative nutrient sources to maintain energy and protein intake.
• Administration of a commercially available enzyme substitute.
• Maintenance of calcium and vitamin D intake.

Clinical Manifestations of Listeria monocytogenes Infection

Listeria monocytogenes is an important bacterial pathogen in neonates, immunosuppressed patients, elderly adults, pregnant women, and occasionally, previously healthy individuals.

Febrile gastroenteritis

• Listeria account for less than one percent of reported cases of bacterial foodborne infections, but outbreaks of febrile gastroenteritis from contaminated food have been described.
• Febrile gastroenteritis secondary to listerial infection typically occurs after ingestion of a large inoculum of bacteria from contaminated food.
• Common symptoms include fever, watery diarrhea, nausea, vomiting, headache, and pains in joints and muscles.
• The typical duration of symptoms is two days or less and recovery is generally complete.
• Invasive infection seems to be rare, with the risk being greatest in immunocompromised, pregnant, or elderly patients.

Infection in pregnancy

• Listeriosis in pregnancy occurs most commonly during the third trimester.
• Fever, chills, and back pain may occur as presenting features of listeriosis in pregnant women; a nonspecific flu-like illness is the most common presentation.
• The infection may be mild, resolve without therapy, and the diagnosis missed if blood cultures are not obtained.
• Listerial infection in pregnant women can lead to fetal death, premature birth, or infected newborns.

Sepsis of unknown origin

• Listerial sepsis occurs in patients of all ages.
• Neonates probably acquire infection during or after birth. Infection in the first week of life is usually manifested by sepsis, while disease manifestations after the first week are more variable and often include meningitis.
• Listeria meningoencephalitis most often occurs in neonates after three days of age and in immunocompromised and elderly adults.
• Adults with Listeria sepsis, most of whom are either immunocompromised or elderly, typically present with fever and chills.
• Septic shock can develop and there may be seeding of the brain and/or meninges, leading to meningoencephalitis or cerebritis.

CNS infection

• The most common central nervous system manifestation of listerial infection is meningoencephalitis. Cerebritis, which infrequently progresses to brain abscess, and rhombencephalitis (brainstem encephalitis) are less common.
• The clinical presentation of Listeria meningoencephalitis ranges from a mild illness with fever and mental status changes to a fulminant course with coma.
• The clinical presentation of cerebritis ranges from fever and headache to hemiplegia, resembling a stroke.
• Rhombencephalitis often follows a biphasic course, beginning with headache, fever, nausea and vomiting, followed in several days by cranial nerve palsies, ataxia, tremor, and other cerebellar signs, decreased consciousness, and possibly seizures and hemiparesis. Almost one-half develop respiratory failure.

Resumed from UptoDate

RIFLE Criteria for Acute Kidney Injury (Renal Failure)

The RIFLE criteria consists of three graded levels of injury (Risk, Injury, and Failure) based upon either the magnitude of elevation in serum creatinine or urine output, and two outcome measures (Loss and End-stage renal disease). 

The RIFLE criteria are as follows :

• Risk — 1.5-fold increase in the serum creatinine or GFR decrease by 25 percent or urine output <0.5 mL/kg per hour for six hours.
• Injury — Twofold increase in the serum creatinine or GFR decrease by 50 percent or urine output <0.5 mL/kg per hour for 12 hours.
• Failure — Threefold increase in the serum creatinine or GFR decrease by 75 percent or urine output of <0.5 mL/kg per hour for 24 hours, or anuria for 12 hours.
• Loss — Complete loss of kidney function (eg, need for renal replacement therapy) for more than four weeks.
• ESRD — Complete loss of kidney function (eg, need for renal replacement therapy) for more than three months. 

Metformin in the Treatment of Diabetes Mellitus

In the absence of contraindications, metformin is considered the first choice for oral treatment of type 2 diabetes. A 2006 consensus statement from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD), updated in 2009, proposed that metformin therapy (in the absence of contraindications) be initiated, concurrent with lifestyle intervention, at the time of diabetes diagnosis.

MECHANISM OF ACTION

• Metformin is effective only in the presence of insulin, and its major effect is to decrease hepatic glucose output.
• In addition, metformin increases insulin-mediated glucose utilization in peripheral tissues (such as muscle and liver), particularly after meals, and has an antilipolytic effect that lowers serum free fatty acid concentrations, thereby reducing substrate availability for gluconeogenesis.
• As a result of the improvement in glycemic control, serum insulin concentrations decline slightly.

EFFICACY
Monotherapy

• Metformin typically lowers fasting blood glucose concentrations by approximately 20 percent and A1C by 1.5 percent, a response similar to that achieved with a sulfonylurea.
• In those who are obese, metformin promotes modest weight reduction or at least weight stabilization. This is in contrast to the weight gain often associated with insulin or sulfonylurea treatment.
• Metformin is less likely to cause hypoglycemia than sulfonylureas and insulin.
• It has lipid-lowering activity, resulting in a decrease in serum triglyceride and free fatty acid concentrations, a small decrease in serum low-density-lipoprotein (LDL) cholesterol concentrations, and a very modest increase in serum high-density-lipoprotein (HDL) cholesterol concentrations.

Combination therapy

• Combinations of drugs are often necessary to achieve optimal glycemic control.
• Metformin can be given in combination with sulfonylureas, insulin, glinides, alpha-glucosidase inhibitors, thiazolidinediones, exenatide, and DPP-IV inhibitors.

SIDE EFFECTS

• The most common side effects of metformin are gastrointestinal, including: metallic taste in the mouth, mild anorexia, nausea, abdominal discomfort, and soft bowel movements or diarrhea. 
• These symptoms are usually mild, transient, and reversible after dose reduction or discontinuation of the drug.
• The dose and duration of use of metformin correlates with the risk of vitamin B12 deficiency due to reduce absorption in the ileum.

PHARMACOLOGY

• Onset of action: Within days; maximum effects up to 2 weeks.
• Distribution: Vd: 654 ± 358 L; partitions into erythrocytes.
• Protein binding: Negligible.
• Metabolism: Not metabolized by the liver.
• Bioavailability: Absolute: Fasting: 50% to 60%.
• Half-life elimination: Plasma: 4-9 hours.
• Time to peak, serum: 
• Immediate release: 2-3 hours; 
• Extended release: 7 hours (range: 4-8 hours).
• Excretion: Urine (90% as unchanged drug; active secretion) .

DOSAGE FORMS

• Metformin is available as 500, 850, or 1000 mg tablets, and should be taken with meals.
• Extended release tablets are also available.
• Combination tablets of metformin and sulfonylureas, thiazolidinediones, or DPP-IV inhibitors are also available.

DOSING

• Begin with 500 mg once daily with the evening meal and, if tolerated, add a second 500 mg dose with breakfast.
• The dose can be increased slowly (one tablet every one to two weeks) as necessary.
• The usual effective dose is 1500 to 2000 mg/day per day. 
• The maximum dose of 2550 mg/day (850 mg TID) provides only marginally better glycemic control and is often not tolerated due to GI side effects.

Resumed from UptoDate.

Cockcroft-Gault Equation

The Cockcroft-Gault equation allows the creatinine clearance to be estimated from the serum creatinine in a patient with a stable serum creatinine:

                                      (140 - age)  x  lean body weight [kg]

CCr (mL/min)    =    —————————————————————————

                                       Cr [mg/dL]  x  72

This formula takes into account the increase in creatinine production with increasing weight, and the decline in creatinine production with age. 

For women, the formula requires multiplication by 0.85 to account for smaller muscle mass compared to men. 

The equation is not adjusted for body surface area. Therefore to compare normal values, the calculation should be adjusted for body surface area. Normalization for body surface increases the accuracy of this equation, particularly among those with decreased renal function. 

Clinical Manifestation of Asthma in Children

Symptoms

• coughing
• wheezing
• shortness of breath or rapid breathing
• chest tightness

Exacerbating factors

• viral infections
• exposure to allergens and irritants (smoke, strong odors, fumes)
• exercise
• emotions
• change in weather/humidity

Aggravating factors

• rhinosinusitis
• gastroesophageal reflux
• sensitivity to nonsteroidal anti-inflammatory drugs (especially aspirin)

Physical examination 

During acute episodes

• tachypnea
• tachycardia
• cough
• wheezing
• a prolonged expiratory phase

As the attack progresses

• cyanosis
• diminished air movement
• retractions
• agitation
• inability to speak
• tripod sitting position
• diaphoresis
• pulsus paradoxus (decrease in blood pressure with inspiration of >15 mm Hg)

Other atopic diseases may observed

• eczema
• allergic rhinitis

Reference:

Nelson Essential of Pediatrics 6th Edition

Risk Factors for Persistent Asthma

Allergy

Atopic dermatitis

Allergic rhinitis

Elevated total serum IgE levels (first year of life)

Peripheral blood eosinophilia >4% (2-3 yr of age)

Food and inhalant allergen sensitization

Gender

Boys

Transient wheezing

Persistent allergy-associated asthma

Girls

Asthma associated with obesity and early-onset puberty

Triad asthma (adulthood)

Parental asthma

Lower respiratory tract infection

Respiratory syncytial virus, parainfluenza

Severe bronchiolitis (e.g., requiring hospitalization)

Pneumonia

Environmental tobacco smoke exposure (including prenatal)

Reference:
Nelson Essential of Pediatrics 6th Edition

Types of Ingredients in Moisturizers for Topical Skin Care

Barrier repair

• Ceramides
• Cholesterol
• Fatty acids

Humectants

• α-Hydroxy acids
• Glycerin
• Hyaluronic acid
• Propylene glycol
• Sodium hyaluronate
• Sorbitol
• Sugars
• Urea  

Occlusives

• Petrolatum
• Mineral oil 
• Paraffin
• Squalene
• Dimethicone
• Soybean oil
• Grapeseed oil
• Propylene glycol
• Lanolin
• Beeswax

References :
Fitzpatrick's Dermatology in General Medicine 7th Edition

Trace Elements: Physiology, Deficiency, Excess and Dietary Sources

Micronutrients include vitamins and trace elements. By definition, a trace element is <0.01% of the body weight. Trace elements have a variety of essential functions.

ELEMENT	PHYSIOLOGY	EFFECTS OF DEFICIENCY	EFFECTS OF EXCESS	DIETARY SOURCES
Chromium	Potentiates the action of insulin	Impaired glucose tolerance, peripheral neuropathy and encephalopathy	Unknown	Meat, brewer's yeast
Copper	Absorbed via specific intestinal transporter; circulates bound to ceruloplasmin; enzyme cofactor (superoxide dismutase, cytochrome oxidase, and enzymes involved in iron metabolism and connective tissue formation)	Microytic anemia, osteoporosis, neutropenia, neurologic symptoms, depigmentation of hair and skin	Acute:nausea, emesis, abdominal pain, coma, and hepatic necrosis; chronic toxicity (liver and brain injury) occurs in Wilson disease and another genetic disorder and secondary to excess intake	Oysters, nuts, liver, margarine, legumes, corn oil
Fluoride	Incorporated into bone	Dental caries	Chronic:dental fluorosis water	Toothpaste, fluoridated water
Iodine	Component of thyroid hormone	Hypothyroidism	Hypothyroidism and goiter; maternal excess may cause congenital hypothyroidism and goiter	Saltwater fish, iodized salt
Iron	Component of hemoglobin, myoglobin, cytochromes, and other enzymes	Anemia, decreased alertness, impaired learning	Acute: nausea, vomiting, diarrhea, abdominal pain, and hypotension; chronic excess usually secondary to hereditary disorders; causes organ dysfunction	Deficiency may also result from blood loss (hookworm infestation, menorrhagia)
Manganese	Enzyme cofactor	Hypercholesterolemia, weight loss, decreased clotting proteins	Neurologic manifestations, cholestatic jaundice	Nuts, grains, tea
Molybdenum	Enzyme cofactor (xanthine oxidase and others)	Tachycardia, tachypnea, night blindness, irritability, coma	Hyperuricemia and increased risk of gout	Legumes, grains, liver
Selenium	Enzyme cofactor (prevents oxidative damage)	Cardiomyopathy (Keshan disease), myopathy	Nausea, diarrhea, neurologic manifestations, nail and hair changes, garlic odor	Meat, seafood, whole grains, garlic
Zinc	Enzyme cofactor; constituent of zinc finger proteins, which regulate gene transcription	Decreased growth, dermatitis of extremities and around orifices, impaired immunity, poor wound healing, hypogonadism, diarrhea; supplements beneficial in diarrhea and improve neurodevelopmental outcomes	Abdominal pain, diarrhea, vomiting; may worsen copper deficiency	Meat, shellfish, whole grains, legumes

Reference:
Nelson Textbook of Pediatrics 18th Edition

Clinical & Laboratory Features of Kawasaki Disease

Kawasaki disease (KD), formerly known as mucocutaneous lymph node syndrome and infantile polyarteritis nodosa, is an acute febrile vasculitis of childhood. It causes severe vasculitis of all blood vessels but predominantly affects the medium-sized arteries, with a striking predilection for the coronary arteries.

The cause of the illness remains unknown, but epidemiologic and clinical features strongly support an infectious origin. These features include the young age group affected, epidemics with wavelike geographic spread of illness, the self-limited nature of the acute febrile illness, and the combination of clinical features of fever, rash, enanthem, conjunctival injection, and cervical lymphadenopathy.

EPIDEMIOLOGIC CASE DEFINITION (CLASSIC CLINICAL CRITERIA)

• Fever persisting at least 5 days
• Presence of at least 4 principal features:
• Changes in extremities
• Acute: Erythema of palms, soles; edema of hands, feet
• Subacute: Periungual peeling of fingers, toes in weeks 2 and 3
• Polymorphous exanthem
• Bilateral bulbar conjunctival injection without exudate
• Changes in lips and oral cavity: Erythema, lips cracking, strawberry tongue, diffuse injection of oral and pharyngeal mucosae
• Cervical lymphadenopathy (>1.5 cm diameter), usually unilateral
• Exclusion of other diseases with similar findings

OTHER CLINICAL AND LABORATORY FINDINGS

• Cardiovascular findings
• Congestive heart failure, myocarditis, pericarditis, valvular regurgitation
• Coronary artery abnormalities
• Aneurysms of medium-size noncoronary arteries
• Raynaud phenomenon
• Peripheral gangrene
• Musculoskeletal system
• Arthritis, arthralgia
• Gastrointestinal tract
• Diarrhea, vomiting, abdominal pain
• Hepatic dysfunction
• Hydrops of gallbladder
• Central nervous system
• Extreme irritability
• Aseptic meningitis
• Sensorineural hearing loss
• Genitourinary system
• Urethritis/meatitis
• Other findings
• Erythema, induration at BCG inoculation site
• Anterior uveitis (mild)
• Desquamating rash in groin

LABORATORY FINDINGS IN ACUTE KAWASAKI DISEASE

• Leukocytosis with neutrophilia and immature forms
• Elevated erythrocyte sedimentation rate (ESR)
• Elevated C-reactive protein (CRP)
• Anemia
• Abnormal plasma lipids
• Hypoalbuminemia
• Hyponatremia
• Thrombocytosis after week 1
• Sterile pyuria
• Elevated serum transaminases
• Elevated serum gamma glutamyl transpeptidase
• Pleocytosis of cerebrospinal fluid

Reference: 

Nelson Textbook of Pediatrics 18th Edition

Classification of Parenteral & Oral Cephalosporins

Cephalosporins differ structurally from penicillins by having the β-lactam ring as a 6 member ring, compared to the 5 member ring structure of the penicillins. These agents are widely used in pediatric practice, both in oral and parenteral formulations. 

The 1st generation cephalosporins are commonly used for management of skin and soft tissue infections caused by susceptible strains of S. aureus and group A streptococcus. 

The 2nd generation cephalosporins have better activity against gram-negative infections than do 1st generation cephalosporins and are used to treat respiratory tract infections, urinary tract infections, and soft-tissue infections. A variety of orally administered 2nd generation agents (cefaclor, cefprozil, loracarbef, cefpodoxime) are commonly used in the outpatient management of sinopulmonary infections. 

The 3rd generation cephalosporins are used for serious pediatric infections, including meningitis and sepsis. Ceftazidime is highly active against most strains of P. aeruginosa, making this a useful agent for febrile, neutropenic oncology patients. 

Another class of 4th generation cephalosporins is indicated for treatment of pediatric meningitis, has activity against P. aeruginosa, and retains good activity against methicillin-susceptible staphylococcal infections.

Cephalosporins	1st Generation	2ndGeneration	Cephamycins	3rd Generation	4th Generation
Parenteral	Cefazolin	Cefamandole	Cefmetazole	Cefoperazole	Cefepime
	Cephalothin	Cefonicid	Cefotetan	Cefotaxime	Cefpirome
	Cephapirin	Cefuroxime	Cefoxitin	Ceftazidime
	Cephradine			Ceftizoxime
				Ceftriaxone
Oral	Cefadroxil	Cefaclor		Cefdinir
	Cephalexin	Cefprozil		Cefditoren
	Cephradine	Cefuroxime-axetil		Cefixime
		Loracarbef		Cefpodoxime
				Ceftibuten

Reference:
Nelson Textbook of Pediatrics 18th Edition

Partial Listing of Drug Interactions of Potential Importance in Pediatric Practice

When 2 or more drugs are administered to the same patient, the pharmacokinetic and pharmacodynamic properties of each agent may be modified by their interaction. Drugs may interact by a number of mechanisms classified on the basis of pharmaceutics, pharmacokinetics, pharmacodynamics, or a combination thereof. These interactions may result in unpredictable clinical effects or toxicologic responses. 

Pharmaceutic interactions include those resulting in drug inactivation when compounds are mixed together physically before patient administration, as with the use of syringes, infusion tubing, dialysate solutions, or parenteral fluid preparations.

Pharmacokinetic interactions can occur when the disposition characteristics of 1 compound (absorption, distribution, metabolism, excretion, or a combination thereof) are influenced by those of another.

Drugs may interact pharmacodynamically and compete for the same receptor or physiologic system, thus altering a patient's response to drug therapy.

INTERACTING AGENT	ADVERSE EFFECT
ACETAMINOPHEN
Alcohol	Hepatotoxicity
Oral anticoagulants	↑ Anticoagulation
Probenecid	↑ Acetaminophen toxicity
Zidovudine	Granulocytopenia
ACYCLOVIR
Narcotics	↑ Narcotic toxicity?
Zidovudine	Lethargy
ALCOHOL
Antidepressants (tricyclic)	↑ Toxicity
Barbiturates	↑ CNS depression (acute)
Benzodiazepines	↑ CNS depression
Cephalosporins (not all)	Disulfiram effect
Chloral hydrate	↑ CNS depression
Doxycycline	↓ Antibiotic effect
Isoniazid	↑ Hepatotoxicity
Metronidazole	Disulfiram effect
Phenothiazines	Impaired coordination
Phenytoin	↑ Phenytoin toxicity
ALLOPURINOL
Aluminum hydroxide	↓ Allopurinol absorption
Ampicillin	Rash
Anticoagulants (oral)	↑ Anticoagulant effect
Azathioprine	↑ Azathioprine toxicity
Captopril	↑ Cutaneous hypersensitivity
Cyclophosphamide	↑ Cyclophosphamide toxicity
Theophylline	↑ Theophylline toxicity
Thiazide diuretics	↑ Allopurinol toxicity
AMINOGLYCOSIDE ANTIBIOTICS
Amphotericin B	↑ Nephrotoxicity
Bumetanide	↑ Ototoxicity
Cisplatin	↑ Nephrotoxicity
Cyclosporine	↑ Nephrotoxicity
Furosemide	↑ Nephrotoxicity and ototoxicity
Magnesium	↑ Neuromuscular blockade
Neuromuscular blocking agents	↑ Blockade
Vancomycin	↑ Nephrotoxicity?
ANTACIDS
β-Adrenergic blockers	↓ Absorption
Captopril	↓ Absorption
Cimetidine	↓ Absorption
Corticosteroids	↓ Absorption
Digoxin	↓ Absorption
Iron	↓ Absorption
Isoniazid	↓ Absorption
Ketoconazole	↓ Absorption
Nonsteroidal anti-inflammatory agents	↓ Absorption
Phenytoin	↓ Absorption
Salicylates	↓ Absorption
Tetracycline	↓ Absorption
Theophylline	↑ Toxicity
ASPIRIN
Anticoagulants (oral)	↑ Bleeding
Captopril	↓ Antihypertensive effect
BARBITURATES
Anticoagulants (oral)	↓ Anticoagulation
β-Adrenergic blockers	↓ β Blockade
Carbamazepine	↑ Production of carbamazepine epoxide
Chloramphenicol	↑ Barbiturate toxicity
Contraceptives (oral)	↓ Contraception
Corticosteroids	↓ Steroid effect
Influenza vaccine (viral)	↑ Barbiturate toxicity
Rifampin	↓ Barbiturate effect
Theophylline	↓ Theophylline effect
Valproate	↑ Barbiturate toxicity
BLEOMYCIN
Oxygen	↑ Pulmonary toxicity
CAPTOPRIL
Allopurinol	↑ Cutaneous hypersensitivity
Aspirin	↓ Antihypertensive effect
Cimetidine	Neuropathy
Nonsteroidal anti-inflammatory agents	↓ Antihypertensive effect
Potassium	Hyperkalemia
Spironolactone	Hyperkalemia
CARBAMAZEPINE
Anticoagulants (oral)	↓ Anticoagulation
Antidepressants (tricyclic)	↑ Toxicity (both drugs)
Cimetidine	↑ Carbamazepine toxicity
Contraceptives (oral)	↓ Contraception
Corticosteroids	↓ Steroid effect
Cyclosporine	↓ Cyclosporine effect
Erythromycins	↑ Carbamazepine toxicity
Influenza vaccine (viral)	↑ Carbamazepine toxicity
Isoniazid	↑ Toxicity (both drugs)
Phenytoin	↓ Carbamazepine effect
Theophylline	↓ Theophylline effect
Valproate	↓ Valproate effect
CIMETIDINE
Alcohol	↑ Alcohol effect
Antacids	↓ Cimetidine effect
Anticoagulants (oral)	↑ Anticoagulation
Antidepressants (tricyclic)	↑ Antidepressant toxicity
Benzodiazepines	↑ Benzodiazepine toxicity
β-Adrenergic blocking agents	↑ β-Blockade toxicity
Captopril	Neuropathy
Carbamazepine	↑ Carbamazepine toxicity
Digoxin	↑ Digoxin toxicity
Ketoconazole	↓ Ketoconazole absorption
Metoclopramide	↓ Cimetidine effect
Phenytoin	↑ Phenytoin toxicity
Theophylline	↑ Theophylline toxicity
CONTRACEPTIVES (ORAL)
Anticoagulants (oral)	↓ Anticoagulation
Antidepressants (tricyclic)	↑ Antidepressant toxicity
Barbiturates	↓ Contraception
Carbamazepine	↓ Contraception
Griseofulvin	↓ Contraception
Penicillins (ampicillin, oxacillin)	↓ Contraception?
Phenytoin	↓ Contraception
Rifampin	↓ Contraception
Theophylline	↑ Theophylline toxicity
CYCLOSPORINE
Alkylating agents	↑ Nephrotoxicity
Aminoglycosides	↑ Nephrotoxicity
Amphotericin B	↑ Nephrotoxicity
Carbamazepine	↓ Cyclosporine effect
Erythromycins	↑ Cyclosporine toxicity
Furosemide	Gout
Ketoconazole	↑ Nephrotoxicity
Metoclopramide	↑ Cyclosporine toxicity
Nafcillin	↓ Cyclosporine effect
Phenytoin	↓ Cyclosporine effect
Rifampin	↓ Cyclosporine effect
DIGOXIN
Antacids	↓ Absorption
Anticholinergics	↑ Digoxin toxicity
Cholestyramine	↓ Absorption
Cimetidine	↑ Digoxin toxicity
Diuretics (hypokalemia)	↑ Digoxin toxicity
Phenytoin	↓ Digoxin effect
Quinidine	↑ Digoxin toxicity
Verapamil	↑ Digoxin toxicity
ERYTHROMYCINS
Anticoagulants (oral)	↑ Anticoagulation
Astemizole (Hismanal)	↑ Astemizole toxicity: arrhythmias
Carbamazepine	↑ Carbamazepine toxicity
Cyclosporine	↑ Cyclosporine toxicity
Phenytoin	↓ Phenytoin effect
Terfenadine (Seldane)	↑ Terfenadine toxicity: arrhythmias
Theophylline	↑ Theophylline toxicity
FLUOROQUINOLONES
Antacids	↓ Antibiotic effect
Theophylline	↑ Theophylline toxicity
GRISEOFULVIN
Anticoagulants (oral)	↓ Anticoagulants
Contraceptive (oral)	↓ Contraceptive
ISONIAZID
Alcohol	Hepatitis
Antacids	↓ Isoniazid absorption
Carbamazepine	↑ Toxicity (both)
Ketoconazole	↓ Ketoconazole effect
Phenytoin	↑ Phenytoin toxicity
Rifampin	↑ Hepatotoxicity
Valproate	↑ Hepatic and CNS toxicity
KETOCONAZOLE
Antacids	↓ Absorption
Anticoagulants (oral)	↑ Anticoagulation
Cimetidine	↓ Ketoconazole effect
Cyclosporine	↑ Nephrotoxicity
Isoniazid	↓ Ketoconazole effect
Phenytoin	Altered metabolism of both drugs
Rifampin	↑ Effects of both drugs
METHOTREXATE
Blood transfusion	↑ Toxicity
Cisplatin	↑ Methotrexate toxicity
Etretinate	↑ Hepatotoxicity
Nonsteroidal anti-inflammatory drugs	↑ Methotrexate toxicity
Trimethoprim/sulfamethoxazole	Megaloblastic anemia
METOCLOPRAMIDE
Carbamazepine	Neurotoxicity
Cimetidine	↓ Cimetidine effect
Cyclosporine	↑ Cyclosporine toxicity
Digoxin	↓ Absorption
Narcotics	↑ Sedation
NIFEDIPINE
β-Adrenergic blockers	Heart failure, atrioventricular block
Cyclosporine	↑ Gingival hyperplasia
Phenytoin	↑ Phenytoin toxicity
Prazosin	Hypotension
Quinidine	↓ Quinidine effect
PHENYTOIN
Alcohol	↑ Toxicity (acute)
Antacids	↓ Phenytoin effect
Anticoagulants (oral)	↓ Phenytoin toxicity, ↑↓ anticoagulation
Antidepressants (tricyclic)	↑ Phenytoin toxicity
Carbamazepine	↓ Carbamazepine effect
Chloramphenicol	↑ Toxicity (both drugs)
Cimetidine	↑ Phenytoin toxicity
Contraceptives (oral and implant)	↓ Contraception
Corticosteroids	↓ Corticosteroid effect
Cyclosporine	↓ Cyclosporine effect
Digoxin	↓ Digoxin effect
Dopamine	Hypotension
Folic acid	↓ Phenytoin effect
Isoniazid	↑ Phenytoin toxicity
Miconazole	↓ Phenytoin effect
Neuromuscular blocking agents	↓ Blockade
Nifedipine	↑ Phenytoin toxicity
Quinidine	↓ Quinidine effect
Rifampin	↓ Phenytoin effect
Theophylline	↓ Effects (both drugs)
Valproate	↑ Phenytoin toxicity
QUINIDINE
Amiodarone	↑ Quinidine toxicity
Anticoagulants (oral)	↑ Anticoagulation
Barbiturates	↓ Quinidine effect
Cimetidine	↑ Quinidine toxicity
Digoxin	↑ Digoxin toxicity
Metoclopramide	↓ Quinidine effect
Phenytoin	↓ Quinidine effect
Procainamide	↑ Procainamide toxicity
Rifampin	↓ Quinidine effect
Verapamil	Hypotension
RIFAMPIN
Anticoagulants (oral)	↓ Anticoagulation
Barbiturates	↓ Barbiturate effect
β-Adrenergic blockers	↓ β Blockade
Chloramphenicol	↓ Chloramphenicol effect
Contraceptives (oral)	↓ Contraception
Corticosteroids	↓ Corticosteroid effect
Cyclosporine	↓ Cyclosporine effect
Isoniazid	↑ Hepatotoxicity
Ketoconazole	↓ Effects (both drugs)
Phenytoin	↓ Phenytoin effect
Quinidine	↓ Quinidine effect
Theophylline	↓ Theophylline effect
Verapamil	↓ Verapamil effect
THEOPHYLLINE
Barbiturates	↓ Theophylline effect
β-Adrenergic blockers	↑ Theophylline toxicity
Carbamazepine	↓ Theophylline effect
Cimetidine	↑ Theophylline toxicity
Erythromycins	↑ Theophylline toxicity
Fluoroquinolones	↑ Theophylline toxicity
Influenza vaccine (viral)	↑ Theophylline toxicity
Interferon	↑ Toxicity?
Marijuana smoking	↓ Theophylline effect
Phenytoin	↓ Effect (both drugs)
Rifampin	↓ Theophylline effect
Tobacco smoking	↓ Theophylline effect
Troleandomycin	↑ Theophylline toxicity
TRIMETHOPRIM/SULFAMETHOXAZOLE
Anticoagulants (oral)	↑ Anticoagulation
Antidepressants (tricyclic)	Depression
Mercaptopurine	↓ Antileukemia effect
Methotrexate	Megaloblastic anemia
VALPROATE
Barbiturates	↑ Phenobarbital toxicity
Benzodiazepines	↑ Diazepam toxicity
Carbamazepines	↓ Valproate effect
Cimetidine	↑ Valproate toxicity?
Ethosuximide	↑ Ethosuximide toxicity?
Phenytoin	↑ Phenytoin toxicity

Reference:
Nelson Textbook of Pediatrics 18th Edition

Diseases Associated with Childhood Obesity

Overweight results from a dysregulation of caloric intake and energy expenditure. A complex interplay between each individual's genetic predispositions and the environment affects an intricate system that controls appetite and energy expenditure.

SYNDROME	MANIFESTATION
Alström syndrome	Hypogonadism, retinal degeneration, deafness, diabetes mellitus
Bardet-Biedl syndrome	Retinal degeneration, syndactyly, polydactyly, hypogonadism, mental retardation, autosomal recessive
Carpenter syndrome	Polydactyly, syndactyly, cranial synostosis, mental retardation
Cohen syndrome	Midchildhood-onset obesity, short stature, prominent maxillary incisors, hypotonia, mental retardation, microcephaly, decreased visual activity
Cushing syndrome	Adrenal hyperplasia or pituitary tumor
Deletion 9q 34	Early-onset obesity, mental retardation, brachycephaly, synophrys, prognathism, behavior and sleep disturbances
ENPP1 gene mutations	Insulin resistance, childhood obesity, chromosome 6q
Fröhlich syndrome	Hypothalamic tumor
Hyperinsulinism	Nesidioblastosis, pancreatic adenoma, hypoglycemia, Mauriac syndrome (poor diabetic control)
Leptin or leptin receptor gene mutation	Early-onset severe obesity, infertility (hypogonadotropic hypogonadism); uncommon;leptin deficiency treatable with recombinant leptin
Melanocortin 4 receptor gene mutation	Early-onset severe obesity, increased linear growth, hyperphagia, hyperinsulinemia; homozygous worse than heterozygous; common genetic cause of obesity
Muscular dystrophy	Late-onset obesity due in part to inactivity
Myelodysplasia	Spina bifida due in part to inactivity
Prader-Willi syndrome	Neonatal hypotonia, normal growth immediately after birth, small hands and feet, mental retardation, hypogonadism; some have partial deletion of chromosome 15 and loss of paternally expressed genes; hyperphagia leading to severe childhood obesity; ghrelin paradoxically elevated
Pro-opiomelanocortin deficiency	Obesity, red hair, adrenal insufficiency, hyperproinsulinemia
Pseudohypoparathyroidism	Variable hypocalcemia, cutaneous calcifications
Turner syndrome	Ovarian dysgenesis, lymphedema, web neck, XO chromosome

Reference:
Nelson Textbook of Pediatrics 18th Edition

Clinical Features of Rickets

Rickets, a disease of growing bone, occurs in children only before fusion of the epiphyses, and is due to unmineralized matrix at the growth plates.

GENERAL

Failure to thrive    Listlessness    Protuding abdomen    Muscle weakness (especially proximal)    Fractures

HEAD

Craniotabes    Frontal bossing    Delayed fontanelle closure    Delayed dentition; caries    Craniosynostosis

CHEST

Rachitic rosary    Harrison groove    Respiratory infections and atelectasis

BACK

Scoliosis    Kyphosis    Lordosis

EXTREMITIES

Enlargement of wrists and ankles    Valgus or varus deformities    Windswept deformity (combination of valgus deformity of 1 leg with varus deformity of the other leg)    Anterior bowing of the tibia and femur    Coxa vara    Leg pain

HYPOCALCEMIC SYMPTOMS

Tetany    Seizures    Stridor due to laryngeal spasm

Reference:
Nelson Textbook of Pediatrics 18th Edition

Causes of Rickets Disease

VITAMIN D DISORDERS

Nutritional vitamin D deficiency

Congenital vitamin D deficiency

Secondary vitamin D deficiency

Malabsorption

Increased degradation

Decreased liver 25-hydroxylase

Vitamin D–dependent rickets type 1

Vitamin D–dependent rickets type 2

Chronic renal failure

CALCIUM DEFICIENCY

Low intake

Diet

Premature infants (rickets of prematurity)

Malabsorption

Primary disease

Dietary inhibitors of calcium absorption

PHOSPHORUS DEFICIENCY

Inadequate intake

Premature infants (rickets of prematurity)

Aluminum-containing antacids

RENAL LOSSES

X-linked hypophosphatemic rickets

Autosomal dominant hypophosphatemic rickets

Hereditary hypophosphatemic rickets with hypercalciuria

Overproduction of phosphatonin

Tumor-induced rickets

McCune-Albright syndrome

Epidermal nevus syndrome

Neurofibromatosis

Fanconi syndrome

Dent disease

DISTAL RENAL TUBULAR ACIDOSIS

Reference:
Nelson Textbook of Pediatrics 18th Edition

Physiologic Factors that Influence the Oral Absorption of Medications in Neonate, Infant & Child

PARAMETER	NEONATE	INFANT	CHILD
Gastric acid secretion	Reduced	Normal	Normal
Gastric emptying time	Decreased	Increased	Increased
Intestinal motility	Reduced	Normal	Normal
Biliary function	Reduced	Normal	Normal
Microbial flora	Acquiring	Adult pattern	Adult pattern

Reference:
Nelson Textbook of Pediatrics 18th Edition

MGH Inclusion & Exclusion Criteria for Administering Intravenous Tissue Plasminogen Activator to Adult Patients with Acute Ischemic Stroke

Inclusion Criteria

A significant neurologic deficit expected to result in long-term disability Noncontrast CT scan showing no hemorrhage or well-established new infarct Acute ischemic stroke symptoms with the patient last known well, clearly defined, less than 3 h before rt-PA will be given

Contraindications

SBP greater than 185 or DBP greater than 110 mmHg (despite measures to reduce it) CT findings (intracranial hemorrhage, subarachnoid hemorrhage, or major infarct signs) Platelets less than 100,000, PTT greater than 40 s after heparin use, or PT greater than 15 or INR greater than 1.7, or known bleeding diathesis Recent surgery/trauma (less than 15 d) Seizure at onset (with postictal impairments) Active internal bleeding (less than 22 d) Recent intracranial or spinal surgery, head trauma, or stroke (less than 3 mo) History of intracranial hemorrhage or brain aneurysm or vascular malformation or brain tumor Suspicion of subarachnoid hemorrhage

Warnings (conditions that might lead to unfavorable outcomes)

Stroke severity too mild Rapid improvement Stroke severity—too severe (e.g., NIHSS greater than 22) [Many centers do not exclude patients based on an increased NIHSS alone] Glucose less than 50 or greater than 400 mg/dL Life expectancy less than 1 y or severe comorbid illness or CMO on admission Increased risk of bleeding Subacute bacterial endocarditis Hemostatic defects including those secondary to severe hepatic or renal disease Diabetic hemorrhage retinopathy, or other hemorrhagic ophthalmic conditions Septic thrombophlebitis or occluded AV cannula at seriously infected site Patients currently receiving oral anticoagulants, e.g., warfarin sodium Increased risk of bleeding due to pregnancy Advanced age (increased risk of bleeding) Documented left heart thrombus

From the Massachusetts General Hospital Acute Stroke Services.

Definition of Acute Lung Injury (ALI) & Acute Respiratory Distress Syndrome (ARDS)

ARDS defines a syndrome of acute respiratory failure of diverse etiology, characterized by noncardiogenic pulmonary edema, hypoxemia, and diffuse lung parenchymal consolidations.

ALI defines an early clinical stage of the same syndrome, with a milder degree of hypoxemia.

Acute onset of respiratory distress

Hypoxemia

ALI: PaO2/FiO2 ≤300 mm Hg

ARDS: PaO2/FiO2 ≤200 mm Hg

Bilateral consolidation of chest radiograph

Absence of clinical findings of cardiogenic pulmonary edema

From: American- European Consensus Conference on ARDS.

Various of Spesific Regional Blocks Anesthesia

Interscalene Block

• The most proximal approach, the interscalene block is performed as the brachial plexus courses in the groove between the anterior and middle scalene muscles, traditionally at the level of the cricoid cartilage.
• Advantages of this block include rapid and reliable blockade of the shoulder region as well as relative ease of landmark palpation.
• Disadvantages of this block traditionally include incomplete coverage of the inferior trunk of the plexus; hence, insufficient anesthesia of the ulnar distribution makes it an unreliable block for forearm or hand procedures.

Supraclavicular Block

• A supraclavicular approach to the brachial plexus provides profound anesthesia to the entire arm, making it an appropriate block for most upper extremity procedures.
• Advantages include a compact formation of the plexus at this level and resultant dense blockade of the entire upper extremity.
• Disadvantages include the remote risk of pneumothorax and potential for slower block onset.

Infraclavicular Block

• The infraclavicular (or coracoid) approach is more distal still, at the level of the cords as they course circumferentially around the subclavian artery, providing dense anesthesia to the entire arm to the fingers.
• Advantages : The consistent anatomic relationship between the cords and the vascular structures makes it a predictable and reliable block to perform under ultrasound guidance. The lower anatomic location of this block makes it unlikely to encounter phrenic blockade and therefore makes it a more appropriate block for bilateral procedures.
• Disadvantages : Concern does exist that if the subclavian artery is accidentally punctured in the infraclavicular approach, subsequent compression of the area to tamponade bleeding is difficult.

Axillary Block

• The axillary block, the most distal of the brachial plexus blocks before the nerves leave the sheath and divide into their terminal branches, is perhaps one of the oldest and most traditional regional blocks for hand and wrist surgery.
• Disadvantages : 
• Because the musculocutaneous nerve frequently leaves the sheath proximal to the intended insertion point of this block, frequently a supplemental injection into the body of the coracobrachialis muscle is needed, especially if a forearm tourniquet is planned.
• Major risks for this block are largely related to the close proximity of the axillary artery.
• Risks for minor bruising, tenderness and hematoma.
• Another concern relating to the high vascularity of this area is local anesthetic and systemic toxicity.

Reference:

Green's Operative Hand Surgery 6th Edition