Lung abscess

lung abscess is a pus-filled cavity in the lung surrounded by inflamed tissue and caused by an infection. A common mechanism is aspiration of stomach contents by vomiting and aspiration of part of the vomitus with all the bacteria from the pharynx, or gastrointestinal tract. Infections and neoplasms are the most common causes. The formation of multiple small (<2 cm) abscesses is occasionally referred to as necrotizing pneumonia or lung gangrene. Before the availability of antibiotics, the etiology of a typical abscess was complications after oral surgical procedures (ie, tonsillectomy), resulting in aspiration of infected material into the lungs. Both lung abscess and necrotizing pneumonia are manifestations of a similar pathologic process. The process is usually surrounded by a fibrous reaction, forming the abscess wall. Multiple small abscess formation may occur and is sometimes referred to as necrotising pneumonia. In children, the most vulnerable patients are those with weakened immune systems, malnutrition , or blunt injuries to the chest.
Lung Abscess is defined as a localized suppurative necrotizing collection occurring within the pulmonary parenchyma. Acute abscesses are less than 4-6 weeks old, whereas chronic abscesses are of longer duration. Several processes, either respiratory or systemic, can lead to abscess formation. Most abscesses are primary, meaning they result from necrosis in an existing parenchymal process (usually an infectious pneumonia). Lung abscesses can be classified based on the duration and the likely etiology. Aspiration into the lungs may be due to impaired normal swallowing mechanisms, esophageal disorders (e.g., acid Reflux ), altered consciousness levels, or absent gag reflex. Signs and symptoms usually begin at least 2 weeks before presentation and include cough, hemoptysis, fever, chills, night sweats, anorexia, pleuritic chest pain, and weight loss. The availability of effective antibiotic therapy for primary lung abscess has drastically modified the natural history of the disease and diminished the role of surgery. A pneumonitis develops which progresses to abscess formation over a period of 1–2 weeks.

Causes of Lung Abscess

The comman causes of Lung Abscess include the following :

• A lung abscess is usually caused by bacteria that normally live in the mouth or throat and that are inhaled into the lungs, resulting in an infection.
• Choking/near-drowning/ aspiration.
• Individuals with an inability to protect their airways because of an absent gag reflex, such as during coma, loss of consciousness, or general anesthesia and sedation.
• Severe periodontal disease.
• The remaining cases are caused by a mixture of anaerobic and aerobic (air breathing) bacteria.
• An abscess may occur secondary to carcinoma of the bronchus; the bronchial obstruction causes postobstructive pneumonia, which may lead to abscess formation.
• Stroke / cerebral palsy /cognitive impairment/impaired consciousness leading to increased risk of aspiration.

Symptoms of Lung Abscess

Some sign and symptoms related to Lung Abscess are as follows :

• The patient usually is sick for several weeks or months with a lack of appetite and the resulting weight loss.
• Cough with foul smelling sputum.
• Coughing pus.
• Poor dental hygiene is common.
• Chills and fever.
• Sweating.
• Productive cough.
• Rapid pulse ( heart rate).
• Foul-smelling cough.
• Bluish discoloration of the skin caused by lack of oxygen.

Treatment of Lung Abscess

Here is list of the methods for treating Lung Abscess:

• Lung abscess is treated with a combination of antibiotic drugs, oxygen therapy, and surgery.
• Penicillin intravenously.
• Cefoxitin is a second-generation cephalosporin that has gram-positive, gram-negative, and anaerobic coverage. This agent may be used when a polymicrobial infection is suspected as cause of lung abscess.
• Clindamycin intravenously.
• Standard treatment of an anaerobic lung infection is clindamycin (600 mg IV q8h followed by 150-300 mg PO qid).
• Patients may receive special antibiotics to treat organisms that may live in the mouth.
• Surgery is very rarely required for patients with uncomplicated lung abscesses.

Pleural effusion

Pleural effusion is defined as an abnormal accumulation of fluid in the pleural space. The pleura produces a fluid which acts as a lubricant that helps you to breathe easily, allowing the lungs to move in and out smoothly. The most common causes are disease of the heart or lungs, and inflammation or infection of the pleura. A pleural effusion is an accumulation of fluid between the layers of the membrane that lines the lungs and chest cavity. Approximately 1 million pleural effusions are diagnosed in the United States each year. Pleural effusion itself is not a disease as much as a result of many different diseases. If blood is in the accumulating fluid, the condition is called "hemothorax"; if pus is present, it is called "empyema"; if air enters the space, it is called "pneumothorax"; and if there is chyle (milky fluid consisting of lymph and fat), it is called "chylothorax." When certain disorders occur, excessive pleural fluid may accumulate and cause pulmonary signs and symptoms. Effusions may be the presenting sign of cancer or they may develop after the cancer is diagnosed.
Parietal pleurae cover the inner surface of the thoracic cavity, including the mediastinum, diaphragm, and ribs. Any extra fluid is taken up by blood and lymph vessels, maintaining a balance. A pulmonary embolism is a blood clot that has floated through the bloodstream and lodged in the lungs. There are two types of pleural effusion: the transudate and the exudate. When either too much fluid forms or something prevents its removal, the result is an excess of pleural fluid--an effusion. Thus, there are in fact two layers of pleura between the outer surface of the lung and the chest wall. One is adherent to the lung, whereas the other layer follows the outline of the chest wall. The two layers press up against one another, and in the healthy chest, there is no air or significant fluid between them. Cancer is responsible for 40% of all pleural effusions, which are then called malignant pleural effusions. Blood in the pleural space (hemothorax) usually results from a chest injury. Rarely, a blood vessel ruptures into the pleural space when no injury has occurred, or a bulging area in the aorta (aortic aneurysm) leaks blood into the pleural space. Any significant increase in the quantity of pleural fluid is a pleural effusion.

Causes of Pleural Effusion

• Pericarditis. This is an inflammation of the pericardium, the membrane covering the heart.
• Cirrhosis (hepatic hydrothorax).
• Autoimmune disease such as systemic lupus erythematosus , bleeding (often due to chest trauma), chylothorax (most commonly caused by trauma), and accidental infusion of fluids.
• Intraabdominal abscess.
• The most common causes of transudative pleural effusions in the United States are left ventricular failure , pulmonary embolism , and cirrhosis.
• Asbestos pleural effusion.
• Atelectasis (which may be due to malignancy or pulmonary embolism).
• The most common causes of exudative pleural effusions are bacterial pneumonia , cancer (with lung cancer , breast cancer), viral infection, and pulmonary embolism .

Symptoms of Pleural Effusion

Some sign and symptoms related to Pleural Effusion are as follows:

• The key symptom of a pleural effusion is shortness of breath.
• Hemoptysis.
• Fever and chills, depending on the cause.
• Weight loss.
• The pain may start and remain in one specific area of the chest wall, or it may spread to the shoulder or back.
• Breathlessness.
• A cough that brings up small amounts of blood.
• Hiccups.
• Night sweats.
• Rapid breathing.
• Swelling in several joints.

Treatment of Pleural Effusion

Here is list of the methods for treating Pleural Effusion:

• Rheumatic fever is treated with antibiotics (usually penicillin) to kill strep bacteria, together with aspirin or other anti-inflammatory drugs to reduce inflammation.
• Large pleural effusions, causing severe breathlessness, are drained, by needle in an acute emergency, or otherwise by chest drain inserted under local anaesthetic.
• Tube thoracostomy. A tube is inserted through the chest and into the pleural space to drain pleural fluid. When used alone, recurrence is very common.
• A small pulmonary embolism can be treated with anticoagulants, drugs that thin the blood and prevent future blood clots.
• Therapeutic thoracentesis may be done if the fluid collection is large and causing pressure or shortness of breath.
• Surgical intervention is most often required for parapneumonic effusions.

Pneumothorax

Pneumothorax is defined as a collection of gas in the pleural space that results in complete or partial collapse of the lung. Normally the pressure in the normal pleural sac is sub atmospheric. With leakage of air into the pleural space the pressure approaches atmospheric, which leads to the collapse of the lung. If pressure in a pneumothorax rises above atmospheric as may occur in a one way (ball valve) leak into the pleural space, a tension pneumothorax is present. This is an emergency.
A pneumothorax is defined as free air (pneumo) trapped within the chest cavity (thorax) - but not within the lungs themselves. Pneumothoraces are divided into tension and non-tension pneumathoraces. A pneumothorax may occur for no identifiable reason; doctors call this a spontaneous pneumothorax. Pneumothorax is considered one of the most common forms of thoracic disease and is classified as spontaneous (not caused by trauma), traumatic, or iatrogenic. Pneumothorax may occur after resuscitation of the baby with oxygen with a pressure bag and mask, as a complication of meconium aspiration syndrome , or most often simply spontaneously when the baby takes its first big breaths. It affects close to 9,000 persons in the United States each year- most often among tall, thin men between 20 and 40 years old.  Spontaneous pneumothorax usually occurs when a small weakened area of lung (bulla) ruptures (primary spontaneous pneumothorax). A pneumothorax may become life-threatening if the pressure in your chest prevents the lungs from getting enough oxygen into the blood.
Pneumothorax is one type of lung disorders called air leak syndrome. A baby can have more than one form of air leak. Signs of pneumothorax include respiratory distress in general - grunting, flaring of the nostrils (nares) , and rapid breathing (tachypnea). The intrapleural space is normally just a 'potential space' that exists between two layers of 'pleura' - thin tissue layers, one of which covers lungs, and one of which lines the chest cavity. If a pneumothorax is severe or the baby is otherwise compromised (for example with respiratory distress syndrome), surgical placement of a plastic suction tube may be done to suck out the air as it leaks out into the pleural space around the lung. A non-tension pneumothorax by contrast is a less severe pathology because the air in the pneumothorax is able to escape. A tension pneumothorax results from any lung parenchymal or bronchial injury that acts as a one-way valve and allows free air to move into an intact pleural space but prevents the free exit of that air. Because of the underlying lung disease, the symptoms and outcome are generally worse in secondary spontaneous pneumothorax; the recurrence rate is similar to that of primary spontaneous pneumothorax.

Causes of Pneumothorax

The comman causes of Pneumothorax include the following :

• A pneumothorax is usually caused by an injury to the chest, such as a broken rib or puncture wound.
• Air leaks occur when the alveoli (tiny air sacs) become overdistended and burst.
• Drugs and toxins.
• Chemotherapy for malignancy.
• People who smoke cigarettes are much more likely to suffer a spontaneous pneumothorax than those who don't.
• Tension pneumothorax is caused when excessive pressure builds up around the lung, forcing it to collapse.
• Paraquat poisoning.
• Spontaneous pneumothorax can result from damage to the lungs caused by conditions such as chronic obstructive pulmonary disease (COPD) , asthma , cystic fibrosis , and pneumonia.
• Tension pneumothorax may be the result of blunt trauma with or without associated rib fractures.
• Spontaneous pneumothorax can also occur in people who don't have lung disease.

Symptoms of Pneumothorax

Some sign and symptoms related to Pneumothorax are as follows:

• Sudden sharp chest pain , made worse by a deep breath or a cough.
• Bluish color of the skin caused by lack of oxygen.
• Chest tightness.
• Primary pneumothorax is usually associated with pain and shortness of breath.
• Rapid respiratory rate.
• Secondary pneumothorax in patients with associated lung disease causes severe shortness of breath; pain is also common.
• Easy fatigue.
• Rapid heart rate.
• Splinting - bending over or holding the chest to protect against pain.

Treatment of Pneumothorax

Here is list of the methods for treating Pneumothorax:

• A chest tube ( chest tube insertion ) placed between the ribs into space surrounding the lungs helps clear the air and allows the lung to re-expand.
• Supplemental oxygen may be needed to help air around the lung be reabsorbed more quickly.
• A tension pneumothorax is a contraindication to the use of military antishock trousers.
• A procedure called pleurodesis can help prevent air and fluid buildup around the lungs and prevent collapses.
• High frequency ventilation is sometimes used for babies with PIE.
• Surgery may be needed to prevent recurrent episodes.

Emphysema

Emphysema condition is defined as the distention of the air spaces distal to the terminal bronchioles withdestruction of alveolar septa within the lungs. It is generally present in both lungs. Air sacs distend and rupture to form large emphysematous sacs, which are not available for exchange of oxygen with blood resulting in less oxygen being available for the body.
Emphysema is a chronic lung disease that can get worse over time. The air sacs are unable to completely deflate, and are therefore unable to fill with fresh air to ensure adequate oxygen supply to the body. It's usually caused by smoking. The tiny air sacs in the lungs called alveoli, through which oxygen is absorbed into the bloodstream, lose their natural elasticity, meaning spent air is pushed back out into the lungs. Emphysema and chronic bronchitis are the two most common forms of chronic obstructive pulmonary disease, and they often occur together. In the United States, cigarette smoking is by far the most important risk factor for emphysema. Symptoms of emphysema include shortness of breath, cough and a limited exercise tolerance. In emphysema, there is permanent enlargement of the tiny air sacs in the lungs (called alveoli) due to the destruction of the walls between the small alveoli. Medical scientists have defined emphysema as "a condition of the lung characterized by abnormal, permanent enlargement of airspaces distal to the terminal bronchioles, accompanied by the destruction of their walls, and without obvious fibrosis".
Emphysema is a serious condition and can be life-threatening. Unlike heart disease and other more common causes of death, the death rate for COPD appears to be rising. Two million Americans are affected, largely those who are over age 50. Centrilobular emphysema, the most common of the three, is usually caused by cigarette smoking. This group of diseases ranks as the fourth leading cause of death in the United States. Pathologists recognize three major types of emphysema: localized (distal acinar, paraseptal), centrilobular (centriacinar), and panlobular (panacinar). Emphysema is part of a lung disease known as COPD. When emphysema is advanced, you must work so hard to expel air from your lungs that breathing can consume up to 20 percent of your resting energy. COPD is the fourth most common and the most rapidly increasing cause of death in the United States. As the disease gets worse, breathing becomes more difficult, and it may become hard to carry out everyday activities. Although COPD can be managed, it cannot be cured at this time. Men are more likely than women to develop emphysema, but female cases are increasing as the number of female smokers rises.

Causes of Emphysema

The comman causes of Emphysema include the following :

• Most cases of emphsyema are caused by cigarette smoking. Cigarette smoke reaches deep into the lungs and causes permanent damage .
• Close relatives of people with emphysema are more likely to develop the disease themselves.
• There is some evidence that air pollution can contribute to people getting emphysema, especially if the person also smokes.
• A viral infection may also cause a COPD exacerbation.
• Abnormal airway reactivity, such as bronchial asthma , has been shown to be a risk factor for the development of emphysema.
• A naturally occurring substance in the lungs called alpha-1 antitrypsin may protect against this damage. People with alpha-1 antitrypsin deficiency are at an increased risk for this disease.

Symptoms of Emphysema

Some sign and symptoms related to Emphysema are as follows:

• Shortness of breath is the most common symptom of emphysema.
• Feeling tired (fatigue).
• Losing weight without trying.
• Cough, sometimes caused by the production of mucus, and wheezing may also be symptoms of emphysema.
• Ankle, feet, and leg swelling.
• Destruction of capillaries feeding the alveoli.
• A barrel-shaped chest.
• Destruction of structures supporting the alveoli.
• Swelling of the ankles
• Lethargy or difficulty concentrating
• Wheezing may occur in some patients, particularly during exertion and exacerbations.

Treatment of Emphysema

Here is list of the methods for treating Emphysema:

• The number one treatment for emphysema is to quit smoking and stay away from smoky places .
• There are other treatments for emphysema, including medications, supplemental oxygen, and more.
• Antibiotics may be prescribed when respiratory infections occur. Influenza (flu) vaccines and Pneumovax (pneumonia vaccine) are recommended for people with emphysema.
• Protein therapy. Infusions of AAt may help slow lung damage in people with an inherited deficiency of the protein.
• Medications used to improve breathing include bronchodilators (hand-held inhaler or nebulizer), diuretics, and corticosteroids.
• Low-flow oxygen can be used during exertion, continuously, or at night.
• Lung transplantation is an option for patients with severe disease.

Rhinitis

 

Rhinitis is inflammation and swelling of the mucous membrane of the nose, characterised by a runny nose and stuffiness and usually caused by the common cold or and an allergy.

The nose is the most commonly infected part of the upper airways. Rhinitis may be acute or chronic. Acute rhinitis commonly results from viral infections but may also be a result of allergies or other causes. Chronic rhinitis usually occurs with chronic sinusitis (chronic rhinosinusitis).

Viral Rhinitis

• Acute viral rhinitis (the common cold) can be caused by a variety of viruses
• Symptoms consists of runny nose, congestion, post nasal drip, cough, and a  low-grade fever.
• Stuffiness can be relieved by taking phenylephrine as a nasal spray or pseudphedrine by mouth. These drugs, available by over the counter, cause the blood vessels of the nasal mucous membrane to constrict. Nasal spray should only be used for only 3 or 4 days because  after that period of time, when the effects of the drugs wear off, the mucous membrane often swells even more that before. This phenomena is called as rebound congestion.
• Antihistamines help  control runny nose but cause drowsiness and other problems, especially in older people.
• Antibiotics are not effective for acute viral rhinitis.

Allergic Rhinitis

• Allergic rhinitis is caused by a reaction of the body's immune system to an enviromental trigger. The most common environmental triggers include dust, molds, pollens, grasses, trees, and animals.
• Symptoms include sneezing, runny nose, stuffiness, and itchy, watery eyes.
• A doctor may diagnose  allergic rhinitis based on a person's history of symptoms. Often, the person has a family history of allergies.More detailed information may be obtained using blood tests or skin testing.
• Avoiding the substance that triggers the allergy prevents symptoms but is often not possible.
• Nasal corticosteroid sprays decrease nasal inflammation caused by many sources and are relatively safe for long-term use.
• Antihistamine help prevent the allergy reaction and thus symptoms.
• Antihistamines dry the mucous membrane of the nose but many of them also cause sleepiness and other problems, especially in older  people.
• Never ones require a prescription but do not have these side effects.
• Allergy shots (desensitization) help to build long therm tolerance to specific  environmental triggers, but they may take months  or years to become fully effective.
• Antibiotic do not relieve the symptoms of allergic rhinitis.

Atrophic Rhinitis

• Atrophic rhinitis is a form of chronic rhinitis in which  the mucous membrane thins (atropies) and hardens, causing the nasal passages to widen and dry out.
• The cells normally found in the mucous membrane of the nose - cells that secrete mucus and have hairlike projections to move dirt particles out - are replaced by cells like those normally found in the skin.
• The disorder can develop in someone who had sinus surgery in which a significant amount of intranasal structures and mucous membranes were removed. 
• A prolong bacterial infection of the lining of the nose is also a factor.
• Crust form inside  the nose, and an offensive odour develops.
• A person may have recurring severe nosebleeds and can lose his sense of smell (anosmia).
• Treatment is aimed at reducing the crusting, elimination the odour, and reducing infections. 
• Topical antibiotics, such as bacitracin applied  inside the nose, kill bacteria.
• Estrogens and vitamins A and D sprayed into the nose or taken by mouth may reduce crusting by promoting mucosal secretions.
• Other antibiotics, given by mouth or intravenously, may also be helpful.
• Surgery to narrow the nasal passages may reduce crusting became the decreased airflow prevents drying if the thinned mucous membrane

Vasomotor Rhinitis

• Vasomotor rhinitis is a form of chronic rhinitis.
• Nasal stuffiness, sneezing, and a runny nose - common allergic symptoms - occur when allergies do not appear to be present.
• In some people, the nose reacts strongly to irritants, perfumes, and pollution.
• The disorder comes and goes but is worsened by dry air.
• The swollen mucous membrane varies fro bright red to purple.
• Sometimes, people also have slight inflammation of the sinuses.
• When persistent, endoscopy of the nose or CT scan of the sinus is not significant.
• Treatment is aimed at relieving symptoms.
• Avoiding smoke and irritants and using a humidified central heating system or vaporizer to increase humidity may be beneficial.

Computational Chemical Biology

Common human diseases result from the interplay of many genes and environmental factors. Furthermore, a drug rarely acts only on one target but follows a similarly complex interaction with proteins. Therefore, an integrative chemical biology approach is needed to unravel the genetic background of diseases and to provide the best possible medicinal treatment.
The Computational Chemical Biology group at CBS has evolved from the former group of Chemoinformatics, with interest in exploring via computational methods the interplay between small molecules and biological systems.


Current areas of interest include

• Chemogenomics mapping of natural compounds.
• Mapping of the pharmacological space of small molecules based on bioassays.
• Associating drugs and drug candidates to clinical outcomes via therapeutic targets and protein-protein interaction networks.
• Predicting adverse effects of drugs via tissue-specific gene expression data.
• Predicting the activity profiles of new psychoactive drug candidates by building informative drug-target interaction networks.

The overall aim of the research focus of CCB is to elucidate the biological profile of small molecules regarding their targets, off-targets, phenotypic outcome and side-effects via an in-depth understanding of the biological networks that lead to disease and the perturbations on them that can be caused by small molecules.


Data collection

• ~50.000 natural products
• ~200.000 drugs with protein targets and/or disease annotation
• ~20 million molecules

Expertise: molecular modeling, machine learning methods (QSAR, NN, SVM,...), chemogenomics and chemical-biological networks.


Fields

• Transporters, GPCR
• Nuclear receptors
• Metabolism and cytochrome P450
• Toxicity
• Antimicrobial Peptides

Ecology of Infectious Disease

Human diseases
Many disease organisms that threaten humans worldwide have complex life histories that are affected by both human and non-human attributes of the ecosystems in which they occur. For example,

• Lyme disease is carried by ticks that move about on mammal hosts such as deer and mice - environmental parameters that affect these non-human hosts have implications for human exposure to Lyme disease
• Rabies is a disease that is contracted by wildlife and can be passed on to humans. NCEAS researchers have assembled and analyzed an extensive database documenting rabid raccoons, refining predictions of rabies dynamics
• The bacterium causing the gastrointestinal disease cholera is waterborne and associated with microscopic crustaceans - climatic and environmental factors that affect hydrodynamics and the ecology of aquatic food webs can influence the dynamics of cholera
• The brain parasite that causes toxoplasmosis is passed among rats, cats, and humans; in humans, infection is associated with lifelong personality changes that may influence human culture
• NCEAS ecologists have formulated and applied cutting edge approaches in analysis and synthesis of human disease scenarios in recent years, improving our understanding of human disease risk

Disease and ecosystems
Ecologists have a growing awareness of the importance of pathogens and parasites in the evolution and ecology of natural systems.  Researchers at NCEAS have examined the evolutionary relationships between disease organisms and their hosts, as well as more modern alterations of pathogen and parasite dynamics by humans . For example:

• Introduced species have escaped many of the parasites of their native ranges ;
• The removal of predators that normally select sick individuals from prey groups may increase pathogen transmission among their populations, when diseased individuals continue living within groups ;
• Primate researchers have examined the role of social and feeding behavior in moderating infection by sexually transmitted diseases and parasites in non-human primates ;
• Disease is considered to be among the most significant causes of the modern coral reef decline, and warmer temperatures encourage some of the most common diseases on coral reefs ;
• Environmental warming and human activities, such as fishing, may have complex disease effects as warm temperatures seem to favor some pathogens and parasites, while decreasing the prevalence or severity of others , and human activities alter host abundance, behavior and environment

Apoptosis

Apoptosis or programmed cell death is the most common form of cell death in eukaryotic organisms. A faulty regulation of apoptosis can cause human diseases. For example, there is too much apoptosis in HIV infections, in tissue damage by physical or chemical stress or in neurodegenerative diseases. By comparison, too little apoptosis is involved in the formation and progression of cancer. Although our understanding of the basic mechanisms of apoptosis has rapidly grown in the last years, the translation of this new knowledge into clinically relevant, pathophysiological concepts is only progressing slowly.

The clinical research group “Regulation of Apoptosis and its Dysfunction in human Diseases” bundles clinically oriented research activities in the field of apoptosis with the perspective to transfer new findings of basic research into clinical practice. In six sub-projects, cell death signalling pathways in human diseases are examined that are characterised either by a deficiency in apoptosis (cancer) or by an excess in apoptosis (AIDS, neurodegenerative diseases). The clinical research group is a continuation of the long-standing research interest of our department at Ulm University that was funded from 2003 to 2005 as "Landesforschungsschwerpunkt Apoptose" by the state of Baden-Württemberg. The clinical research group is expected to strengthen the research profile of the Medical Faculty at Ulm University.

As shown in the illustration, the cross-project research question is, in which manner pathogenic stimuli like DNA damage (P1-5), death receptor ligands (P4, P5), viral proteins (P6) or pathological protein aggregates (P5) lead to a dysfunction of apoptosis signaling pathways and therefore to an excess or a deficiency of apoptosis, causing human diseases (pathologically increased apoptosis in HIV infection (P6) or neurodegenerative diseases (P5); pathologically reduced apoptosis in cancer (P1-4, 7).

Uncovering the molecular mechanisms which are responsible for the dysfunction of apoptosis in the human diseases investigated will provide the basis for the development of new diagnostic and therapeutic strategies for modulation of apoptosis and for their evaluation in preclinical disease models and with primary material from patients.

Therefore, there is a long-term perspective to transfer the new knowledge on the molecular pathogenesis of human diseases gathered in the clinical research group, namely on the dysfunction of apoptosis signaling pathways, into clinical practice („from bench to bedside“).

illustration: the role of apoptosis signaling pathways in human diseases

Respiratory Failure

Respiratory failure is nearly any condition that affects breathing function or the lungs themselves and can result in failure of the lungs to function properly. The main tasks of the lungs and chest are to get oxygen from the air that is inhaled into the bloodstream, and, at the same to time, to eliminate carbon dioxide (C02) from the blood through air that is breathed out. In respiratory failure, the level of oxygen in the blood becomes dangerously low, and/or the level of C02 becomes dangerously high. There are two ways in which this can happen. Either the process by which oxygen and C02 are exchanged between the blood and the air spaces of the lungs (a process called "gas exchange") breaks down, or the movement of air in and out of the lungs (ventilation) does not take place properly.
Respiratory failure often is divided into two main types. One of them, called hypoxemic respiratory failure, occurs when something interferes with normal gas exchange. Too little oxygen gets into the blood (hypoxemia), and all organs and tissues in the body suffer as a result. One common type of hypoxemic failure, occurring in both adults and prematurely born infants, is respiratory distress syndrome, a condition in which fluid or tissue changes prevent oxygen from passing out of the air sacs of the lungs into the circulating blood. Hypoxemia also may result from spending time at high altitudes (where there is less oxygen in the air); various forms of lung disease that separate oxygen from blood in the lungs; severe anemia ("low blood"); and blood vessel disorders that shunt blood away from the lungs, thus precluding the lungs from picking up oxygen.

The other main type of respiratory failure is ventilatory failure, occurring when, for any reason, breathing is not strong enough to rid the body of C02. Then CO2 builds up in the blood (hypercapnia). Ventilatory failure can result when the respiratory center in the brainstem fails to drive breathing; when muscle disease keeps the chest wall from expanding when breathing in; or when a patient has chronic obstructive lung disease that makes it very difficult to exhale air with its C02. Many of the specific diseases and conditions that cause respiratory failure cause both too little oxygen in the blood (hypoxemia) and abnormal ventilation.
Several different abnormalities of breathing function can cause respiratory failure. The major categories, with specific examples of each, are:

Obstruction of the airways. Examples are chronic bronchitis with heavy secretions; emphysema; cystic fibrosis; asthma (a condition in which it is very hard to get air in and out through narrowed breathing tubes).

Weak breathing. This can be caused by drugs or alcohol, which depress the respiratory center; extreme obesity; or sleep apnea, where patients stop breathing for long periods while sleeping.

Muscle weakness. This can be caused by a muscle disease called myasthenia; muscular dystrophy; polio; a stroke that paralyzes the respiratory muscles; injury of the spinal cord; or Lou Gehrig's disease.

Lung diseases, including severe pneumonia. Pulmonary edema, or fluid in the lungs, can be the source of respiratory failure. Also, it can often be a result of heart disease; respiratory distress syndrome; pulmonary fibrosis and other scarring diseases of the lung; radiation exposure; burn injury when smoke is inhaled; and widespread lung cancer.

An abnormal chest wall (a condition that can be caused by scoliosis or severe injury of the chest wall).

A majority of patients with respiratory failure are short of breath. Both low oxygen and high carbon dioxide can impair mental functions. Patients may become confused and disoriented and find it impossible to carry out their normal activities or do their work. Marked C02 excess can cause headaches and, in time, a semi-conscious state, or even coma. Low blood oxygen causes the skin to take on a bluish tinge. It also can cause an abnormal heart rhythm (arrhythmia). Physical examination may show a patient who is breathing rapidly, is restless, and has a rapid pulse. Lung disease may cause abnormal sounds heard when listening to the chest with a stethoscope: wheezing in asthma, "crackles" in obstructive lung disease. A patient with ventilatory failure is prone to gasp for breath, and may use the neck muscles to help expand the chest.
The symptoms and signs of respiratory failure are not specific. Rather, they depend on what is causing the failure and on the patient's condition before it developed. Good general health and some degree of "reserve" lung function will help see a patient through an episode of respiratory failure. The key diagnostic determination is to measure the amount of oxygen, carbon dioxide, and acid in the blood at regular intervals. A sudden low oxygen level in the lung tissue may cause the arteries of the lungs to narrow. This, in turn, causes the resistance in these vessels to increase, which can be measured using a special catheter. A high blood level of C02 may cause increased pressure in the fluid surrounding the brain and spinal cord; this, too, can be measured.
Nearly all patients are given oxygen as the first treatment. Then the underlying cause of respiratory failure must be treated. For example, antibiotics are used to fight a lung infection, or, for an asthmatic patient, a drug to open up the airways is commonly prescribed.

A patient whose breathing remains very poor will require a ventilator to aid breathing. A plastic tube is placed through the nose or mouth into the windpipe and is attached to a machine that forces air into the lungs. This can be a lifesaving treatment and should be continued until the patient's own lungs can take over the work of breathing. It is very important to use no more pressure than is necessary to provide sufficient oxygen; otherwise ventilation may cause further lung damage. Drugs are given to keep the patient calm, and the amount of fluid in the body is carefully adjusted so that the heart and lungs can function as normally as possible. Steroids, which combat inflammation, may sometimes be helpful but they can cause complications, including weakening the breathing muscles.

The respiratory therapist has a number of methods available to help patients overcome respiratory failure. They include:

Suctioning the lungs through a small plastic tube passed through the nose, in order to remove secretions from the airways that the patient cannot cough up.

Postural drainage, in which the patient is propped up at an angle or tilted to help secretions drain out of the lungs. The therapist may clap the patient on the chest or back to loosen the secretions, or a vibrator may be used for the same purpose.

Breathing exercises often are prescribed after the patient recovers. They make the patient feel better and help to strengthen the muscles that aid breathing. One useful method is for the patient to suck on a tube attached to a clear plastic hosing containing a ball so as to keep the ball lifted. Regular deep breathing exercises are simpler and often just as helpful. Another technique is to have the patient breathe out against pursed lips to increase pressure in the airways and keep them from collapsing.
The outlook for patients with respiratory failure depends chiefly on its cause. If the underlying disease can be effectively treated, with the patient's breathing supported in the meantime, the outlook is usually good.

Care is needed not to expose the patient to polluting substances in the atmosphere while recovering from respiratory failure; this could tip the balance against recovery. When respiratory failure develops slowly, pressure may build up in the lung's blood vessels, a condition called pulmonary hypertension. This condition may damage the vessels, worsen hypoxemia, and cause the heart to fail. If it is not possible to provide enough oxygen to the body, complications involving either the brain or the heart may prove fatal.

If the kidneys fail or the diseased lungs become infected, the prognosis is worse. In some cases, the primary disease causing the lungs to fail is irreversible. The patient, family, and physician together then must decide whether to prolong life by ventilator support. Occasionally, lung transplantation is a possibility, but it is a highly complex procedure and is not widely available

Because respiratory failure is not a disease itself, but the end result of many lung disorders, the best prevention is to treat any lung disease promptly and effectively. It is also important to make sure that any patient who has had lung disease is promptly treated for any respiratory infection (even of the upper respiratory tract). Patients with lung problems should also avoid exposure to pollutants, as much as is possible. Once respiratory failure is present, it is best for a patient to receive treatment in an intensive care unit, where specialized personnel and all the needed equipment are available. Close supervision of treatment, especially mechanical ventilation, will help minimize complications that would compound the problem.
A common form of lung disease in which breathing, and therefore gas exchange, is labored and increasingly difficult.

Gas exchange
The process by which oxygen is extracted from inhaled air into the bloodstream, and, at the same time, carbon dioxide is eliminated from the blood and exhaled.

Hypoxemia
An abnormally low amount of oxygen in the blood, the major consequence of respiratory failure, when the lungs no longer are able to perform their chief function of gas exchange.

Pulmonary fibrosis
An end result of many forms of lung disease (especially chronic inflammatory conditions). Normal lung tissue is converted to scarred, "fibrotic" tissue that cannot carry out gas exchange.

Nasal Polyps

A polyp is any overgrowth of tissue from a surface. Polyps come in all shapes--round, droplet, and irregular being the most common. >Nasal polyps tend to occur in people with respiratory allergies. Hay fever (allergic rhinitis) is an irritation of the membranes of the nose by airborne particles or chemicals. These membranes make mucus. When irritated, they can also grow polyps. The nose is not only a passageway for air to reach the lungs; it also provides the connection between the sinuses and the outside world. Sinuses are lined with mucus membranes, just like the nose. Polyps can easily obstruct the drainage of mucus from the sinuses. When any fluid in the body is trapped so it cannot flow freely, it becomes infected. The result, sinusitis, is a common complication of allergic rhinitis.

Some people who are allergic to aspirin develop both asthma and nasal polyps.

Nasal polyps often plug the nose, usually one side at a time. People with allergic rhinitis are so used to having a stopped up nose they may not notice the difference when a polyp develops. Other polyps may be closer to a sinus opening, so airflow is not obstructed, but mucus becomes trapped in the sinus. In this case, there is a feeling of fullness in the head, no sense of smell, and perhaps a headache. The trapped mucus will eventually get infected, adding pain, fever, and perhaps bloody discharge from the nose.

A physical examination will identify most polyps. Small polyps located higher up or further back may be hidden from view, but they will be detected with more sophisticated medical instruments. The otorhinolaryngologist is equipped to diagnose nasal polyps. In order to perform the exam, medicine must be applied to decongest the membranes. Cotton balls soaked with one of these agents and left in the nostrils for a few minutes provide adequate shrinkage.

Most polyps can be removed by the head and neck surgeon as an office procedure called a nasal polypectomy. Bleeding, the only complication, is usually easy to control. Nose and sinus infections can be treated with antibiotics and decongestants, but if airflow is restricted, the infection will reoccur.
If aspirin is the cause, all aspirin containing medications must be avoided.

Since most nasal polyps are the result of allergic rhinitis, they can be prevented by treating this condition. New treatments have greatly improved control of hay fever. There are now several spray medicines that are quite effective. Spray cortisone-like drugs are the most popular. Over-the-counter nasal decongestants have an irritating effect similar to the allergy they are supposed to be treating. Continued use can bring more trouble than relief and result in an addiction to nose sprays. The resulting disease, rhinitis medicamentosa, is more difficult to treat than allergic rhinitis.

Allergists and ENT surgeons both treat allergic rhinitis with a procedure called desensitization. After identifying suspect allergens using one of several methods, they will give the patient increasing doses of those allergens in order to produce blocking antibodies that will impede the allergic reaction. This is effective in a number of patients, but the treatment may take a period of months to years. Allergen
Any substance that irritates only those who are sensitive (allergic) to it.

Asthma
Wheezing (labored breathing) due to allergies or irritation of the lungs.

Decongestant
Medicines that shrink blood vessels and consequently mucus membranes. Pseudoephedrine, phenylephrine, and phenylpropanolamine are the most common.

Sinus
Air-filled cavities surrounding the eyes and nose are lined with mucus-producing membranes. They cleanse the nose, add resonance to the voice, and partially determine the structure of the face.

Lung Cancer

Lung Cancer is the leading cause of cancer deaths in both women and men in the United States and throughout the world. Lung cancer is the number one cause of cancer deaths in men and has surpassed breast cancer as the leading cause of cancer deaths in women. In the United States in 2004, 160,440 people were projected to die from lung cancer compared with a projected 127,210 deaths from colorectal, breast, and prostate cancer combined. Only about 14% of all people who develop lung cancer survive for 5 years.
Cancer occurs when normal cells undergo a transformation that causes them to grow and multiply without the normal controls. The cells form a mass or tumor that differs from the surrounding tissues from which it arises. Tumors are dangerous because they take oxygen, nutrients, and space from healthy cells.

Most lung tumors are malignant. This means that they invade and destroy the healthy tissues around them.

The tumors can also spread to nearby lymph nodes or through the bloodstream to other organs. This process is called metastasis.

When lung cancer metastasizes, the tumor in the lung is considered the primary tumor, and the tumors in other parts of the body are called secondary tumors or metastatic tumors.

Some lung tumors are metastatic from cancers elsewhere in the body. The lungs are a common site for metastasis. Lung cancers are usually divided into 2 groups that account for about 95% of all cases.

The division is based on the type of cells that make up the cancer.

The 2 types of lung cancer are classified based on the cell size of the tumor. They are called small cell lung cancer (SCLC) and non–small cell lung cancer (NSCLC). NSCLC includes several more types of tumors.

SCLCs are less common, but they grow more quickly and are more likely to metastasize than NSCLCs. Often, SCLCs have already spread to other parts of the body when the disease is diagnosed.

About 5% of lung cancers are of rare cell types, such as carcinoid tumor, lymphoma, or metastatic (cancers from other parts of the body that spread to the lungs). The specific types of primary lung cancers are as follows:

Adenocarcinoma (an NSCLC) is the most common type of lung cancer, making up 30-40% of all cases. A subtype of adenocarcinoma is called bronchoalveolar cell carcinoma, which creates a pneumonialike appearance on chest x-ray films.

Squamous cell carcinoma (an NSCLC) is the second most common type of lung cancer, making up about 30% of all lung cancers.

Large cell cancer makes up 10% of all cases.

SCLC makes up 20% of all cases.

Carcinoid Lung Cancer accounts for 1% of all cases.

Laryngitis

Laryngitis is caused by inflammation of the larynx, resulting in hoarseness of the voice.

When air is breathed in (inspired), it passes through the nose and the nasopharynx or through the mouth and the oropharynx. These are both connected to the larynx, a tube made of cartilage. The vocal cords, responsible for setting up the vibrations necessary for speech, are located within the larynx. The air continues down the larynx to the trachea. The trachea then splits into two branches, the left and right bronchi (bronchial tubes). These bronchi branch into smaller air tubes which run within the lungs, leading to the small air sacs of the lungs (alveoli).

Either food, liquid, or air may be taken in through the mouth. While air goes into the larynx and the respiratory system, food and liquid are directed into the tube leading to the stomach, the esophagus. Because food or liquid in the bronchial tubes or lungs could cause a blockage or lead to an infection, the airway must be protected. The epiglottis is a leaf-like piece of cartilage extending upwards from the larynx. The epiglottis can close down over the larynx when someone is eating or drinking, preventing these substances from entering the airway.

In laryngitis, the tissues below the level of the epiglottis are swollen and inflamed. This causes swelling around the area of the vocal cords, so that they cannot vibrate normally. A hoarse sound to the voice is very characteristic of laryngitis. Laryngitis is a very common problem, and often occurs during the course of an upper respiratory tract infection (cold).

Laryngitis - Causes and Symptoms

Laryngitis is caused almost 100% of the time by a virus. The same viruses which cause the majority of simple upper respiratory infections (colds, etc.) are responsible for laryngitis. These include parainfluenzae virus, influenza virus, respiratory syncytial virus, rhinovirus, coronavirus, and echovirus. Extremely rarely, bacteria such as Group A streptococcus, M. catarrhalis, or that which causes tuberculosis may cause laryngitis. In people with faulty immune systems (particular due to acquired immunodeficiency syndrome, or AIDS), infections with fungi may be responsible for laryngitis.

Symptoms usually begin along with, or following, symptoms of a cold. A sore, scratchy throat, fever, runny nose, achiness, and fatigue may all occur. Difficulty swallowing sometimes occurs with streptococcal infections. The patient may cough and wheeze. Most characteristically, the patient's voice will sound strained, hoarse, and raspy.

In extremely rare cases, the swelling of the larynx may cause symptoms of airway obstruction. This is more common in infants, because the diameter of their airways is so small. In that case, the baby may have a greatly increased respiratory rate, and exhibit loud high-pitched sounds with breathing (called stridor).

Laryngitis - Diagnosis

Diagnosis is usually made by learning the history of a cold followed by hoarseness. The throat usually appears red and somewhat swollen. Listening to the chest and back with a stethoscope may reveal some harsh wheezing sounds with inspiration (breathing in).

In long-standing (chronic laryngitis), tuberculosis may be suspected. Using a scope called a laryngoscope, examination of the airway will show redness, swelling, small bumps of tissue called nodules, and irritated pits in the tissue called ulcerations. Special skin testing (TB testing) will reveal that the individual has been exposed to the bacteria causing TB.

Laryngitis - Treatment

Treatment of a simple, viral laryngitis simply addresses the symptoms. Gargling with warm salt water, pain relievers such as acetaminophen, the use of vaporizers to create moist air, and rest will help the illness resolve within a week.

In an infant who is clearly struggling for air, it may be necessary to put in an artificial airway for a short period of time. This is very rarely needed.

An individual with tubercular laryngitis is treated with a combination of medications used to treat classic TB. In people with fungal laryngitis, a variety of anti-fungal medications are available.

Laryngitis - Alternative treatment

Alternative treatments include aromatherapy inhalations made with benzoin, lavender, frankincense, thyme, and sandalwood. Decoctions (extracts made by boiling an herb in water) or infusions (extracts made by steeping an herb in boiling water) can be made with red sage (Salvia officinalis var. rubra) and yarrow (Achillea millefolium) or with licorice (Glycyrrhiza glabra). These are used for gargling, and are said to reduce pain. Echinacea ( Echinacea spp.) tincture taken in water every hour for 48 hours is recommended to boost the immune system. Antiviral herbs, including usnea (Usnea spp.), lomatium (Lomatium dissectum), and ligusticum (Ligusticum porteri), may help hasten recovery from laryngitis. Homeopathic remedies are recommended based on the patient's symptoms. Some people may get relief from placing cold compresses on the throat.

Laryngitis - Prognosis

Prognosis for laryngitis is excellent. Recovery is complete, and usually occurs within a week's time.

Laryngitis - Prevention

Prevention of laryngitis is the same as for any upper respiratory infections. The only way to even attempt to prevent such illnesses is by good handwashing, and by avoiding situations where one might come in contact with people who might be sick. However, even with relatively good hygiene practices, most people will get about five to six colds per year. It is unpredictable which of these may lead to laryngitis.

Key Terms

Epiglottis
A leaf-like piece of cartilage extending upwards from the larynx, which can close like a lid over the trachea to prevent the airway from receiving any food or liquid being swallowed.

Larynx
The part of the airway lying between the pharynx and the trachea.

Nasopharynx
The part of the airway into which the nose leads.

Oropharynx
The part of the airway into which the mouth leads.

Trachea
The part of the airway which leads into the bronchial tubes.

Laryngeal Cancer

Laryngeal cancer is cancer of the larynx or voice box.

The larynx is located where the throat divides into the esophagus and the trachea. The esophagus is the tube that takes food to the stomach. The trachea, or windpipe, takes air to the lungs. The area where the larynx is located is sometimes called the Adam's apple.

The larynx has two main functions. It contains the vocal cords, cartilage, and small muscles that make up the voice box. When a person speaks, small muscles tighten the vocal cords, narrowing the distance between them. As air is exhaled past the tightened vocal cords, it creates sounds that are formed into speech by the mouth, lips, and tongue.

The second function of the larynx is to allow air to enter the trachea and to keep food, saliva, and foreign material from entering the lungs. A flap of tissue called the epiglottis covers the trachea each time a person swallows. This blocks foreign material from entering the lungs. When not swallowing, the epiglottis retracts, and air flows into the trachea. During treatment for cancer of the larynx, both of these functions may be lost.

Cancers of the larynx develop slowly. About 95% of these cancers develop from thin, flat cells similar to skin cells called squamous epithelial cells. These cells line the larynx. Gradually, the squamous epithelial cells begin to change and are replaced with abnormal cells. These abnormal cells are not cancerous but are pre-malignant cells that have the potential to develop into cancer. This condition is called dysplasia. Most people with dysplasia never develop cancer. The condition simply goes away without any treatment, especially if the person with dysplasia stops smoking or drinking alcohol.

The larynx is made up of three parts, the glottis, the supraglottis, and the subglottis. Cancer can start in any of these regions. Treatment and survival rates depend on which parts of the larynx are affected and whether the cancer has spread to neighboring areas of the neck or distant parts of the body.

The glottis is the middle part of the larynx. It contains the vocal cords. Cancers that develop on the vocal cords are often diagnosed very early because even small vocal cord tumors cause hoarseness. In addition, the vocal cords have no connection to the lymphatic system. This means that cancers on the vocal cord do not spread easily. When confined to the vocal cords without any involvement of other parts of the larynx, the cure rate for this cancer is 75% to 95%.

The supraglottis is the area above the vocal cords. It contains the epiglottis, which protects the trachea from foreign materials. Cancers that develop in this region are usually not found as early as cancers of the glottis because the symptoms are less distinct. The supraglottis region has many connections to the lymphatic system, so cancers in this region tend to spread easily to the lymph nodes and may spread to other parts of the body (lymph nodes are small bean-shaped structures that are found throughout the body; they produce and store infection-fighting cells). In 25% to 50% of people with cancer in the supraglottal region, the cancer has already spread to the lymph nodes by the time they are diagnosed. Because of this, survival rates are lower than for cancers that involve only the glottis.

The subglottis is the region below the vocal cords. Cancer starting in the subglottis region is rare. When it does, it is usually detected only after it has spread to the vocal cords, where it causes obvious symptoms such as hoarseness. Because the cancer has already begun to spread by the time it is detected, survival rates are generally lower than for cancers in other parts of the larynx.

About 12,000 new cases of cancer of the larynx develop in the United States each year. Each year, about 3,900 die of the disease. Laryngeal cancer is between four and five times more common in men than in women. Almost all men who develop laryngeal cancer are over age 55. Laryngeal cancer is about 50% more common among African-American men than among other Americans.

Hantaviruses

Hantaviruses, any of several members of the virus family Bunyaviridae that infect vertebrates (animals with backbones, including humans). Unlike most members of this family, which are carried by mosquitoes, ticks, or flies, hantaviruses are carried by specific rodent hosts and are transmitted directly from host to host by virus-laden saliva, urine, and feces. Humans are infected through exposure to the dried excretions from infected rodents. Hantaviruses cause two different human diseases: hemorrhagic fever with renal syndrome, in which damage to the kidneys is common, and acute respiratory distress syndrome, in which damage to the lungs is common.

Hantaviruses are spherical and are 90 to 100 nanometers (1 nanometer equals 1 billionth of a meter, or 4 x 10-8 inches) in diameter. They are composed of an envelope covered with spikes surrounding three protein-wrapped, circular pieces of ribonucleic acid (RNA). Although many hantaviruses have been identified recently, their true number and potential for causing disease is probably far greater than is presently thought.

Acute respiratory distress syndrome is one of two human diseases caused by hantavirus. Dust containing virus-infected rodent feces becomes airborne and is inhaled. The virus embeds in the lungs where the infection begins. Flulike symptoms appear in about a week, followed by the collection of fluid and white blood cells in the lungs, causing respiratory failure, then death.

HANTAAN VIRUS

The first human disease known to be due to a hantavirus infection was hemorrhagic fever with renal syndrome, identified in the early 1950s during the Korean War. Thousands of United Nations troops developed a mysterious disease marked by fever, headache, hemorrhage, and acute kidney failure. Despite much research, the cause remained unknown for 26 years until a new virus, named Hantaan virus, was isolated in Korea from field mice in 1976.

Hemorrhagic fever with renal syndrome is widespread in the Far East, particularly in China and Korea. There are two seasonal disease peaks, associated with the harvesting of wheat in summer and of rice in late fall. During these times the host rodent populations peak and the fields are full of dust containing dried, virus-laden excrement. The disease is fatal in about 5 to 10 percent of cases. A milder form of the disease, caused by Seoul virus and transmitted by rats, occurs in Japan, Korea, China, and the United States, especially in seaports, where rats are common. Symptoms are less severe and include nephritis (inflammation of the kidneys).

SIN NOMBRE VIRUS

In 1993 a new hantavirus disease was recognized in the southwestern United States. The illness was at first referred to as Four Corners Disease, named for the area where the disease was first observed, where Arizona, New Mexico, Colorado, and Utah meet. The agent responsible was called the Sin Nombre (an area in New Mexico which in Spanish means “no name”) virus. The victims of the virus developed influenza-like symptoms—including fever, muscle aches, cough, and headache—which rapidly worsened. Fluid and white blood cells accumulated in the lungs, causing hypoxia (low blood-oxygen levels), shock, and, in many cases, death from a type of lung failure called acute respiratory distress syndrome, also known as hantavirus pulmonary syndrome. Within a short time, cases were found in other states. By the end of 1995, 123 cases, with a fatality rate of 51 percent, had been confirmed from 23 states. The disease was also identified in Canada, Brazil, Venezuela, and Argentina.

The search for the cause of this mysterious disease began with typical epidemiological studies that involved interviewing survivors and people who came in contact with the victims. Blood samples from victims shared evidence of antibodies against hantaviruses, an indication that they had been exposed to hantavirus in the past, and that this earlier exposure had initiated an immune response. To prove which hantavirus was indeed the cause of the victims' death, scientists used the polymerase chain reaction (PCR). This technique is used to rapidly amplify DNA strands. Once amplified, specific methods are used to identify the specific virus. Scientists determined with certainty that hantavirus was present in the tissues of the victims and determined that the disease was caused by a previously unknown hantavirus. Hantavirus specimens from different areas were compared, revealing that several previously unknown viruses were active in the United States. The entire genetic structure of the Sin Nombre virus was determined, and diagnostic tests were created. The same methods are being used in attempts to develop a vaccine. (For a description of vaccines, See Immunization.)

The primary host of Sin Nombre virus in the southwestern United States is the deer mouse, Peromyscus maniculatus. In large sections of this part of the country, 10 to 35 percent of deer mice are infected, and in certain areas about 80 percent of deer mice carry the virus.

Sin Nombre virus, like other hantaviruses, does not cause disease in its rodent hosts. The virus is shed in the saliva, urine, and feces of these animals for many weeks and perhaps for the lifetime of the animal. Human infection occurs when dust containing infected dried rodent excretions is inhaled. Sin Nombre and the other newly discovered hantaviruses probably have long been present in the region of the western United States inhabited by deer mice. The virus was recognized in 1993 only because of the number and clustering of human cases, after two particularly wet winters and an abundant supply of rodent food caused an increase in rodent populations, which then led to a rise in the incidence of the disease.

PREVENTION

The risk of infection by hantaviruses can be reduced by preventing rodents from living in or near human dwellings. Rodent nests and droppings should be wetted down with a disinfectant before they are removed.

Emphysema

Emphysema, progressive respiratory disease characterized by coughing, shortness of breath, and wheezing, developing into extreme difficulty in breathing, and sometimes resulting in disability and death. Although the exact cause is unknown, bronchial spasm, infection, irritation, or a combination of the three seem to be contributory. The highest degree of occurrence is among heavy cigarette smokers, especially those exposed to polluted air. Children who suffer from bronchitis or asthma are also susceptible. In recent years emphysema has become a serious public health problem in terms of rapidly increasing numbers of disabilities and deaths.

In the course of the disease the passages leading to the air sacs of the lungs become narrowed. Air is trapped in the sacs, and the tissues of the lungs lose their natural elasticity and undergo destructive changes. Symptoms akin to the common cold or asthmatic wheezing may result. As the disease progresses the volume of residual air trapped in the lungs increases, and the volume of each breath decreases. The lungs increase in size, and in severe cases the patient develops a characteristic “barrel chest.” The lungs become unable to supply enough oxygen to the body tissues. This reduction in oxygen intake causes the heart to pump faster; consequently, the heart becomes strained. Excessive carbon dioxide in the blood gives the patient a bluish skin color.

Although the deterioration in the lungs brought about by emphysema is permanent and irreversible, treatment can give relief and increase functioning capacity. Abstention from smoking is essential, and change of occupation or residence may be necessary if air pollution or occupational pollution aggravates the condition. Bronchial dilators, special breathing exercises, and antibiotics are also helpful. Therapy is most successful in instances when the disease is diagnosed at an early stage.

The term emphysema is also used to describe infiltration of air into connective tissue and between air cells of the lungs.