10 May 2009

Tinnitus



Tinnitus
Presenatation by:Lianne Beck, MD
Assistant Professor
Emory Family Medicine

Tinnitus
* Definition
* Classification
* Objective tinnitus
* Subjective tinnitus
* Theories
* Evaluation
* Treatment

Introduction
* Tinnitus -“The perception of sound in the absence of external stimuli.”
* Tinnire – means “ringing” in Latin
* Includes buzzing, hissing, roaring, clicking, pulsatile sounds
* For some, an unbearable sound that drives them to contemplate suicide.
* May be perceived as unilateral or bilateral
* Originating in the ears or around the head
* First or only symptom of a disease process or auditory/psychological annoyance

Classification

* Objective tinnitus – sound produced by paraauditory structures which may be heard by an examiner, often pulsatile
* Subjective tinnitus – sound is only perceived by the patient (most common)
* Pulsatile tinnitus – matches pulse or a rushing sound
o Possible vascular etiology
o Objective or subjective
o Increased or turbulent blood flow through paraauditory structures

Objective tinnitus
* Vascular (pulsatile)
o A/V malformations
o Vascular tumors
o Venous hum (cardiac murmurs, anemia, BIH, thyrotoxicosis, pregnancy, dehiscent jugular bulb)
o Atherosclerosis
o Ectopic carotid artery
o Persistent stapedial artery
o Vascular loops
* Neuromuscular
o Palatomyclonus
o Stapedial muscle spasm
* Patulous eustachian tube

Arteriovenous Malformations
* Congenital lesions
* Occipital artery and transverse sinus, internal carotid and vertebral arteries, middle meningeal and greater superficial petrosal arteries
* Mandible
* Brain parenchyma
* Dura
* Pulsatile tinnitus
* Headache
* Papilledema
* Discoloration of skin or mucosa

Vascular tumors
* Glomus tympanicum
o Paraganglioma of middle ear
o Loud pulsatile tinnitus which may decrease with ipsilateral carotid artery compression
o Reddish mass behind tympanic membrane which blanches with positive pressure
o Conductive hearing loss

Vascular tumors
* Glomus jugulare
o Paraganglioma of jugular fossa
o Loud pulsatile tinnitus
o Conductive hearing loss if into middle ear
o Cranial neuropathies

Venous hum
* Benign intracranial hypertension
* Dehiscent jugular bulb
* Transverse sinus partial obstruction
* Increased cardiac output from
o Pregnancy
o Thyrotoxicosis
o Anemia

Benign Intracranial Hypertension
* Also called pseudotumor cerebri
* Young, obese, female patients
* Hearing loss
* Aural fullness
* Dizziness
* Headaches
* Visual disturbance
* Papilledema, pressure >200mm H20 on LP

Benign Intracranial Hypertension
* Sismanis and Smoker 1994
o 100 patients with pulsatile tinnitus
o 42 found to have BIH syndrome
o 16 glomus tumors
o 15 atherosclerotic carotid artery disease
* Treatment
o Weight loss
o Diuretics
o Subarachnoid-peritoneal shunt
o Gastric bypass for weight reduction

Neuromuscular Causes
* Palatal myoclonus
o Clicking sound
o Rapid (60-200 beats/min), intermittent
o Contracture of tensor palantini, levator palatini, levator veli palatini, tensor tympani, salpingopharyngeal, superior constrictors
o Muscle spasm seen orally or transnasally
o Rhythmic compliance change on tympanogram

Myoclonus
Stapedius Muscle Spasm
Patulous Eustachian Tube
Subjective Tinnitus
Conductive hearing loss
Sensorineural hearing loss
Other subjective tinnitus
CNS Mechanisms
Neurophysiologic Model
Role of Depression
Ototoxic Drugs
Evaluation - History
Evaluation – Physical Exam
Evaluation - Audiometry
Laboratory studies
Imaging
Glomus Tympanicum
Glomus jugulare
Acoustic Neuroma
ENT Referral
Treatments
Treatments - Medicines
Treatments
* Hearing aids – amplification of background noise can decrease tinnitus
* Maskers – produce sound to mask tinnitus
* Tinnitus instrument – combination of hearing aid and masker
Conclusions
References

Tinnitus.ppt

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Hematuria



Hematuria

Gross hematuria:
Suspected if a red or brown color change of urine
Intermittent red or brown color urine a/w variety of clinical setting
Medications (phenazopyridine, microbid, NSAID)
Ingestion of beets or certain dyes
Metabolities
Myoglobinuria or hemoglobinuria

Work up
Centrifuge the specimen, Supernatant be tested for heme (hemoglobin or myoglobin) with a urine dipstick.

Causes of heme-negative red urine
Medications
Food dyes
Metabolities
Doxorubicin
Beets (in selected patients)
Bile pigments
Chloroquine
Blackberries
Homogentisic acid
Deferoxamine
Food coloring
Melanin
Ibuprofen
Methemoglobin
Iron sorbitol
Porphyrin
Nitrofurantoin
Tyrosinosis
Phenazopyridine
Urates
Phenolphthalein
Rifampin

Approach to the patient with red or brown urine
Microscopic hematuria:
Major causes of hematuria by age and duration
The evaluation should address the following three questions

1. Are there any clues from the history or physical examination that suggest a particular diagnosis?
2. Does the hematuria represent glomerular or extraglomerular bleeding?
3. Is the hematuria transient or persistent?

Goal is to quickly identify
* Infection
* Kidney stone
* Malignant

History and Physical
Mechanisms by Which Selected Drugs May Cause Hematuria
Hemorrhagic cystitis
Urolithiasis
Carbonic anhydrase inhibitors
Vital sign: BP, T, HR
Abdomen for masses, tenderness (flank, suprapubics), bruits
CVS: irregular irregular
Edema (especially periorbital)
Joint erythema, swelling, warmth
Paleness, jaundice
Careful inspection of external genitalia
Physical Examination Findings and Associated Causes of Hematuria

Physical examination finding
Cause of hematuria
General (systemic) examination
Severe dehydration
Renal vein thrombosis
Peripheral edema
Nephrotic syndrome, vasculitis
Cardiovascular system
Myocardial infarction
Renal artery embolus or thrombus
Atrial fibrillation
Renal artery embolus or thrombus
Hypertension
Glomerulosclerosis with or without proteinuria
Abdomen
Bruit
Arteriovenous fistula
Genitourinary system
Enlarged prostate
Urinary tract infection
Phimosis
Urinary tract infection
Meatal stenosis
Urinary tract infection
Glomerular or Extra Glomerular bleeding?
Microscopic hematuria DDx
Microscopic hematuria DDx
Rare cause of Microscopic Hematuria
Arteriovenous malformations and fistulas
Nutcracker syndrome
Loin pain-hematuria syndrome
Proteinuria
Extraglomerular vs Glomerular in UA
Findings on Microscopy
Transient or persistent hematuria
Exception:
Persistent hematuria
Laboratory Tests (initial work up)
Further Work up
Renal Biopsy
Radiologic and other tests for the evaluation of hematuria
Initial Evaluation of Asymptomatic Microscopic Hematuria
Reference

Hematuria.ppt

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Insulin Secretion, Beta Cell Biology



Insulin Secretion, Beta Cell Biology and the Pathogenesis of Type 2 Diabetes


Kenneth S. Polonsky
Presentation by:Professor of Medicine, Cell Biology and Physiology
Director Institute of Clinical and Translational Sciences
Washington University School of Medicine

Diabetes:Basic Abnormalities
Islets of Langerhans
GLUCOSE
Pancreas
Muscle
Liver
Fat

INSULIN
* The pancreas does not produce enough insulin
* Muscle, liver and fat tissues don’t respond to insulin-insulin resistance
* Elevated Fatty Acids impair insulin secretion and action

Normal Glucose Tolerance
Genetic susceptibility
Diabetogenic Lifestyle
Normal Glucose Tolerance
Insulin Resistance
Compensatory hypersecretion of insulin
Impaired Glucose Tolerance
Insulin Resistance
β-cell compensation starts to fail
Overt Hyperglycemia
Insulin Resistance
Failed β-cell compensation

Pancreatic beta-cell dysfunction in overt type 2 diabetes
* Abnormal insulin secretion
o Absent first phase response to intravenous glucose
o Delayed and blunted response to a mixed meal
o Abnormal insulin secretory oscillations
o Increased levels of proinsulin and proinsulin breakdown intermediates
* Reduced beta cell mass

Glucose infusion rate (mg/kg/min)
Resistant

Intravenous Glucose Infusion in Insulin resistant subjects
Insulin Secretion and Glucose
Lean Control
Failure of insulin secretion to respond to glucose oscillations in IGT
Decreased Insulin Content in Type 2 Diabetes
T2DM=Type 2 diabetes.
Decrease in Beta-Cell Volume in Type 2 Diabetes
Obese
Lean
Conclusions

* Progressive abnormalities in insulin secretion are consistently present as people progress from NGT to IGT to Diabetes.
* Increases in glucose concentrations within the normal range are associated with progressive reductions in insulin secretion.
* Insulin resistance is consistently present along with defects in insulin secretion and results cannot resolve which factor is playing a primary role.

Classification Based on Genetic Mechanism and Age of Clinical Presentation
Monogenic
* Neonatal diabetes
* Diabetes in older children and young adults (MODY)
* Mitochondrial diabetes
Polygenic
* Type 2 Diabetes in adults
Genome Wide Association Studies
Recent Smaller Genome Wide Association Studies
Transcription factor in Wnt pathway
Polygenic type 2 diabetes genes
Mechanism-Beta cell
Genes that cause or are associated with diabetes
Overall summary and conclusions
* Genetic variation at multiple loci contribute to overall diabetes risk and to date account for <5% of diabetes genetic risk.
* The genes identified affect insulin secretion predominantly.
* Insulin secretion is abnormal at all stages in the evolution of type 2 diabetes and in genetically predisposed individuals with normal glucose.
* The complexity of these results have raised questions regarding the feasibility of personalized medicine and at this stage it is not clear if genetic testing will add to clinical management of the majority of diabetic patients.

Glucose Metabolism
* Glucokinase
* Hnf1α
Glucokinase
* The enzyme that phosphorylates glucose to glucose-6-phosphate allowing further metabolism in the glycolytic pathway
* Expressed in the pancreatic beta cell and liver
* Based on knowledge of physiology, mutations would be predicted to cause
o hyperglycemia associated with
o reduced glucose induced insulin secretion
o reduced liver glycogen

Relationship between Glucose and Insulin Secretion Rate
Changes in Hepatic Glycogen content after meals
Effects of mutations that activate or impair glucokinase activity
Summary
* Subjects with E23K polymorphisms in Kir6.2 who have normal blood glucose levels have reduced insulin secretion.
* At this stage insulin sensitivity is enhanced when compared to matched controls.
* This could be a compensatory response to reduced insulin secretion or an effect of the polymorphism on insulin action.
Beta cell survival and mass
Observations from islet isolation
Questions
Decrease in Beta-Cell Volume in Type 2 Diabetes1

Insulin Secretion.ppt

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