Reye’s Syndrome

Reye’s syndrome is a postinfectious triad consisting of encephalopathy, fatty liver degeneration, and transaminase elevation.

• During the 1970s, 300 to 600 cases were being reported yearly in the U.S.
• Since the mid-1980s, after the understanding that aspirin is associated with Reye’s syndrome, the yearly count has fallen to <20 cases
• Seasonal relation with influenza and varicella outbreaks
• Age: rare in persons aged >18 yr; peak age (in the U.S.) is 6 to 8 yr
• Case-fatality rate: 25% to 50%

• Temporal association with influenza and varicella infection
• Epidemiologic association with aspirin or other salicylate use to treat the viral infection
• Possible association with aflatoxin and pesticides
• Pathology

• Liver: no inflammation; the striking finding is panlobular microvesicular hepatocyte infiltration on light microscopy and mitochondrial injury on electron microscopy
• Brain: no inflammation but cerebral edema and anoxic degeneration
• Pathogenesis: not fully understood but mitochondrial dysfunction is clearly center stage

• Inborn errors of metabolism (e.g., carnitine deficiency, ornithine transcarbamylase deficiency)
• Salicylate or amiodarone intoxication
• Jamaican vomiting sickness
• Hepatic encephalopathy of any cause
• Table E1-433 describes diseases that present a clinical or pathologic picture resembling
Reye’s syndrome.

• Elevated transaminase (alanine aminotransferase and aspartate aminotransferase)
• Elevated ammonia level
• Occasional elevation of creatine phosphokinase, lactate dehydrogenase, and bilirubin and prolongation of prothrombin time
• Occasional hypoglycemia (in patients <4 yr)
• Cerebrospinal fluid is normal or contains <8 white blood cells per milliliter
• Rarely a liver biopsy is indicated (in infants or in recurrent cases)

• Supportive
• Mannitol, glycerol, or hyperventilation for cerebral edema if present
• Interferon-alfa (experimental)
• Prevention
 Influenza vaccine
 Varicella vaccine
 Avoidance of aspirin in children, especially during influenza and varicella outbreaks

Retinal Hemorrhage

In a retinal hemorrhage, blood accumulates in or on the surface of the retina, in the subretinal space, or in the vitreous cavity. Generally, these hemorrhages are abnormal and causes should be sought.

• Hemorrhage within the retina or subretinal area
• Evidence of retinal tears, tumors, and inflammation; macular degeneration, drugs, diabetes.

• Diabetes
• Hypertension
• Trauma
• Inflammation
• Tumors
• Subretinal neovascularization
• Associated with diabetes and aging
• Rapid changes in altitude (mountain climbing or scuba diving).

• Evaluate patients for local and systemic diseases.
• Trauma in children or adults
• Venous or arterial occlusion associated with atherosclerotic or heart disease may cause retinal hemorrhage.
• Rule out malignant melanoma, trauma, hypertensive cardiovascular disease.
Section II describes the differential diagnosis of acute painless loss of vision.

• Minimum: complete blood count, erythrocyte sedimentation rate, complete blood chemistries
• Visual field testing
• Usually not necessary
• Trauma: skull radiographs or head CT (evaluate for fractures)
• Ultrasound
• Fluorescein angiography (evaluate retinal vascular diseases and macular degeneration)


• Laser or treatment of underlying disorder
• Treat medical problems (age-related macular degeneration, etc.)
• Laser treatment may be indicated for certain retinal diseases.
• Treatment may be indicated with wet macular degeneration (intravitreal injection).
• Treat underlying disease.
• Repair any damage from trauma.
• Vitamin therapy: high in zinc and antioxidants for macular degeneration
• Treatment will differ depending on various causes of bleeding.
• Encourage adequate control of underlying medical disorders.

Renal Vein Thrombosis

Renal vein thrombosis is the thrombotic occlusion of one or both renal veins.

• Incidence unknown; probably an underdiagnosed condition
• May occur at any age with no gender preference
• Epidemiology tied to the underlying cause.

Acute bilateral renal vein thrombosis:
• Back and bilateral flank pain
• Acute renal failure
Acute unilateral renal vein thrombosis:
• Flank pain
• Decline in renal function
• Hematuria
• Increase in the amount of proteinuria if associated with nephrotic syndrome
Chronic unilateral renal vein thrombosis:
• May be silent
• Pulmonary emboli and hemolysis
• Back pain
• Deep vein thrombosis in lower extremities
• Edema
• Glycosuria
• Hyperchloremic acidosis
• Left varicocele (if the left renal vein is thrombosed)
• Dilated abdominal veins

The diagnosis of renal vein thrombosis does not include any differential consideration. The differential diagnosis is that of proteinuria. Renal vein thrombosis should be considered if proteinuria worsens or if renal function worsens
in a patient with glomerulonephritis. Renal vein thrombosis should also be considered in patients with pulmonary emboli and no lowerextremity deep vein thrombosis.


• Anticoagulation in acute renal vein thrombosis to prevent pulmonary emboli and in attempt to improve renal function and decrease proteinuria
• Thrombolytic therapy or surgical thrombectomy has also been reported to be effective
• The value of anticoagulation in chronic renal vein thrombosis is dubious except in nephrotic patients with membranous glomerulonephritis with profound hypoalbuminemia where prolonged prophylactic anticoagulation
may be of benefit even if renal vein thrombosis has not been documented.

Renal Cell Adenocarcinoma

Renal cell adenocarcinoma (RCA) is a primary adenocarcinoma originating in the renal parenchyma from the malignant transformation of proximal renal tubular epithelial cells. Most renal cell cancers are of clear cell type. Papillary tumors comprise 15% of renal cancers, and chromophobe tumors make up 10%.

Hereditary forms:
• Familial renal carcinoma
• Renal carcinoma associated with von Hippel- Lindau disease
• Hereditary papillary renal cell carcinoma
Risk factors:
• Cigarette smoking
• Obesity

• Use of diuretics
• Phenacetin-containing analgesics
• Asbestos exposure
• Gasoline and other petroleum products
• Lead
• Cadmium
• Thorotrast
• Role of the VHL gene on chromosome 3

• Transitional cell carcinomas of the renal pelvis (8% of all renal cancers)
• Wilms’ tumor
• Other rare primary renal carcinomas and sarcomas
• Renal cysts
• All causes of hematuria (see Section II)
• Retroperitoneal tumors
Laboratory tests and imaging studies.
• Urinalysis: hematuria
• Complete blood count: anemia or erythrocytosis
• Nonmetastatic hepatic dysfunction with elevated alkaline phosphatase, prolonged prothrombin time, and hypoalbuminemia
• Hypercalcemia (caused by parathyroid-related protein)
• Other: elevated ferritin, elevated insulin and glucagon levels, elevated alpha-fetoprotein, and elevated beta–human chorionic gonadotropin
• Recent reports indicate that urine AQP1 and ADFP concentrations quantified by Western
blot appear to be sensitive and specific biomarkers of kidney cancers of proximal tubule origin and may be useful to diagnose an imaged renal mass and screen for kidney cancer at an early stage. Additional investigations are under way to determine if these tests should become standard tumor markers in the investigation of renal masses.

Nearly 50% of renal cancers are now detected because a renal mass is incidentally detected
on radiographic evaluation.
• Renal ultrasound
• Abdominal CT scan with contrast ; CT-guided biopsy is generally not necessary for diagnosis of solid masses >4 cm (high likelihood of cancer)
• Renal arteriogram
• Intravenous pyelography


• Surgery C Surgical nephrectomy (open procedure or laparoscopic approach) is the only effective management for stages I, II, and some stage III tumors. Although radical nephrectomy had long been the standard
treatment, retrospective studies have shown that partial rather than radical nephrectomy is associated with improved
survival and is appropriate for patients with renal cell neoplasms <4 cm that are not adjacent to renal pelvis.
C Various forms of partial nephrectomy may be available for patients with bilateral
cancers or with a solitary kidney.
C The role of nephrectomy in patients with metastatic renal cell carcinoma is controversial and should probably be reserved for patients who have a solitary metastasis amenable to surgical resection. However, there are data showing that nephrectomy before immunotherapy improves survival in patients with metastatic renal cell cancer compared with immunotherapy alone.
• Angioinfarction (for palliation)
• Radiotherapy (for palliation)
• Chemotherapy: In patients with unresectable disease, inhibitors of vascular endothelial growth factor (VEGF) such as the antivascular endothelial growth factor antibody bevacizumab, mTOR kinase inhibitors such
as everolimus and temsirolimus, and the tyrosine kinase inhibitors axitinib, sunitinib, pazopanib, and sorafenib can be used as first-line therapy.
• Hormonal therapy (high-dose progesterone may achieve a 15% to 20% response rate)
• Immunotherapy: interleukin-2 may achieve a 15% to 30% response rate; alpha-, beta-, and gamma-interferons are somewhat less effective and now used less frequently.


Rabies is a fatal zoonotic illness caused by the rabies virus and transmitted to human beings by the bite of an infected animal

• Incubation period of 10 to 90 days
1. Shorter incubation period with bites on the face. In domestic animals the incubation period is generally 3 to 12 weeks but can range from several days to months, rarely exceeding 6 months
2. Longer if extremities involved
• Prodrome
1. Fever
2. Headache
3. Malaise
4. Pain or anesthesia at exposure site
5. Sore throat
6. Gastrointestinal symptoms
7. Psychiatric symptoms

• Acute neurologic period, with objective evidence of central nervous system involvement
1. Extreme hyperactivity and bizarre behavior alternating with periods of relative calm
2. Hallucinations, disorientation
3. Seizures
4. Paralysis
5. Fear, pain, and spasm of the pharynx and larynx caused by drinking
6. Coma, death

• Delirium tremens
• Tetanus
• Hysteria
• Psychiatric disorders
• Other viral encephalitides
• Guillain-Barré syndrome
• Poliomyelitis.
• The direct fluorescent antibody (DFA) test is the gold standard for rabies diagnosis.
Animals submitted for rabies testing should be euthanized in a way that maintains the integrity of the brain
• Negri bodies are eosinophilic cytoplasmic inclusions found in neurons. They are the best-known histologic feature of rabies
• The national case definition for animal rabies requires laboratory confirmation by either:
1. A positive DFA test (preferably performed on CNS tissue); or
2. Isolation of rabies virus (in cell culture or in a laboratory animal)

• Isolation of the patient to prevent transmission to others
• Supportive therapy
• No known beneficial therapy. A case report from 2005 describes a 15-yr-old girl who survived rabies and had been treated with a combination of ketamine, midazolam, ribavirin, and amantadine. It is known as the
Milwaukee protocol. The protocol has been unsuccessful in subsequent reports and is considered investigative.• Emphasis is placed on prophylaxis of potentially exposed individuals after an exposure:
1. Thorough wound cleansing and irrigation of the wound with soap and water as soon as possible. If available, a virucidal agent (e.g., povidine-iodine solution) should be used to irrigate the wounds.
2. Active and passive immunization is most effective when used within 72 hr of exposure.
• Vaccinations: The CDC has recently recommended reducing the number of vaccine
doses for postexposure prophylaxis. Current recommendations for rabies postexposure
prophylaxis are as follows:
1. Human diploid cell vaccine (HDCV) or purified chick embryo cell vaccine (PCECV) 1  ml IM (deltoid area) 1 each on days 0, 3, 7, and 14 in patients not previously vaccinated.
In patients previously vaccinated administer HDCV or PCECV 1 ml IM (deltoid area) 1 each on days 0 and 3. Human
rabies hyperimmune globulin (RIG) 20 IU/kg body weight should be administered to persons not previously vaccinated. If anatomically feasible, the full dose should be infiltrated into the wound; any remaining volume should be given IM at a site separate from vaccine administration.
• Preexposure prophylaxis with HDCV or RVA (1 ml IM on days 0, 7, and 21 or 28) in individuals at high risk for acquisition:
1. Veterinarians
2. Laboratory workers working with rabies virus
3. Spelunkers
4. Visitors to endemic areas


Psoriasis is a chronic skin disorder characterized by excessive proliferation of keratinocytes, resulting in the formation of thickened scaly plaques, itching, and inflammatory changes of the epidermis and dermis. The various forms of psoriasis include guttate, pustular, and arthritis variants.

● The primary psoriatic lesion is an erythematous papule topped by a loosely adherent scale . Scraping the
scale results in several bleeding points (Auspitz sign).
● Chronic plaque psoriasis generally manifests with symmetrical, sharply demarcated, erythematous, silver-scaled
patches affecting primarily the intergluteal folds, elbows, scalp, fingernails, toenails, and knees . This form
accounts for 80% of psoriasis cases.
● Psoriasis can also develop at the site of any physical trauma (sunburn, scratching). This is known as Koebner’s
● Nail involvement is common (pitting of the nail plate), resulting in hyperkeratosis, and onychodystrophy, with
onycholysis .
● Pruritus is variable.
● Joint involvement can result in sacroiliitis and spondylitis.
● Guttate psoriasis is generally preceded by streptococcal pharyngitis and manifests with multiple droplike lesions on
the extremities and trunk .

● Unknown
● Familial clustering (genetic transmission with a dominant mode with variable penetrants)
● One third of persons affected have a positive family history.
● Within the past decade, several putative loci for genetic susceptibility to psoriasis have been reported. One locus (psoriasis susceptibility 1 [PSORS1] locus) in the major histocompatibility complex (MHC) region on chromosome 6 is considered the most important susceptibility locus.

● Generally not necessary for diagnosis
● Diagnosis is clinical.
● Skin biopsy is rarely necessary.

● Sunbathing generally leads to improvement.
● Eliminate triggering factors (e.g., stress, certain medications [lithium, beta blockers, antimalarials]).
● Patients with psoriasis benefi t from a daily bath in warm water followed by the application of a cream or ointment
moisturizer. Regular use of an emollient moisturizer limits evaporation of water from the skin and allows the stratum
corneum to rehydrate itself.
● Therapeutic options vary according to the extent of disease. Approximately 70% to 80% of all patients can be treated adequately with topical therapy.
● Patients with limited disease (less than 20% of the body) can be treated with topical steroids, calcipotriene, tar products, anthralin, and retinoids.
● Therapeutic options for persons with generalized disease (affecting more than 20% of the body) include UVB light
exposure three times weekly and oral PUVA. Systemic treatment includes methotrexate and cyclosporine for severe
psoriasis. Chronic plaque psoriasis may be treated with alefacept, a recombinant protein that selectively targets
T lymphocytes or etanercept, a tumor necrosis factor (TNF) antagonist.



■ Most systems require an anterior approach to the ankle. Place the patient supine on the operating table with the
foot near the end of the table. Place a small bump or lift under the ipsilateral hip to help place the ankle straight
and avoid the tendency of the leg to externally rotate.
■ After induction of general anesthesia, apply and inflate a thigh tourniquet to control bleeding and improve

■ Any significant deformity above or below the ankle joint must be corrected before placement of the total ankle
■ The approach is determined by the prosthesis design, and the reader is referred to the specific implant chosen.

however, most systems require an anterior approach to the ankle.
■ Make an incision from about 10 cm proximal to the ankle joint on the lateral side of the tibialis tendon, over
the flexor hallucis tendon. This incision is medial to the most medial major branch of the superficial peroneal
nerve, the dorsal medial cutaneous nerve. Often a very small medial branch of this nerve crosses the incision
just distal to the ankle joint and must be incised for exposure. The patient should be warned before surgery
that a small area of numbness may be present just medial to the incision.
■ Open the flexor hallucis longus sheath and retract the tendon medially. Retract the neurovascular bundle containing the anterior tibial artery, vein, and deep peroneal nerve laterally with the extensor digitorum longus

■ Make a straight incision in line with the skin incision in the ankle capsule, and reflect the capsule medially until
the medial ankle gutter is exposed and laterally until the lateral gutter is exposed.
■ Expose the dorsal talonavicular joint and remove any anterior, medial, or lateral osteophytes. If better exposure
of the joint line is needed, use an osteotome to perform a more aggressive removal of the anterior
■ Prepare the bone for implant insertion according to the technique guide specific for the implant selected, with
care taken to place the implant in proper alignment in all planes and to have sufficient bone coverage of the prosthesis and proper tensioning of the soft tissues and ligamentous support after the final implant. There should be a balance between choosing a thicker polyethylene insert (better for wear characteristics) and excessive bone resection and joint motion and stability.
■ Close the capsule over the prosthesis and insert a closed suction drain; close the superior extensor retinaculum
over the flexor hallucis longus sheath, and close the skin in layers.
■ A popliteal block is routinely used for postoperative analgesia.


At our institution, patients are typically kept overnight in the hospital and are seen by a physical therapist the following day for instruction in gait training with touch-down weight bearing. Therapy with antibiotics, binasal cannula oxygen, and deep venous thrombosis prophylaxis with low-molecular-weight heparin is the normal postoperative protocol, although this is not typically continued after discharge unless the patient has risk factors for deep venous thrombosis. Different implants have different recommendations for postoperative care, but we typically delay weight bearing for 4 to 6 weeks and begin active ankle motion once the incision is healed, typically 2 weeks after surgery. Gradual progressive weight bearing, calf strengthening, proprioceptive training, and range-of-motion exercises are started at 4 to 6 weeks, with the ankle protected in a prefabricated walking boot. A light ankle brace is applied at 8 to 10 weeks, and full activities are allowed at 3 months, or when the calf muscles are fully rehabilitated. No restrictions are placed on the patients’ activities or sports programs, but they are encouraged to avoid impact exercises for conditioning.