Clinical Instructor, Department of Pathology and Laboratory Medicine, University of Cincinnati College of
Medicine, Cincinnati, Ohio
Noisetrauma Cochlear damage can occur withdrawal symptoms order pristiq 100mg with visa, for example medications during childbirth order 100mg pristiq, from shooting without ear protectors or from industrialnoise(seep treatment plan buy 50 mg pristiq otc. Acousticneuroma this is a slow-growing benign schwannoma of the vestibular nerve (see p medicine 3605 v buy pristiq 100 mg without a prescription. The presence of otalgia treatment brown recluse spider bite cheap pristiq 50 mg amex, otorrhoea medications varicose veins buy pristiq 100 mg with mastercard, tinnitus or hearing loss suggests an otologic aetiology medications help dog sleep night order pristiq 50mg otc. Positional vertigo is precipitated by head movements treatment xerostomia order pristiq 50 mg free shipping, usually to a particularposition,andoftenoccurswhenturninginbedoronsittingup. The vertigo lasts seconds (<1 minute) and the phenomenon becomes less severe on repeated movements (fatigue). There is no serious underlying cause but it sometimesfollowsvestibularneuronitis(seep. Ifthediseasecannot be controlled, then a chemical labyrinthectomy, perfusing the round window orifice with ototoxic drugs such as gentamicin, is used. Gentamicin destroys the vestibular epithelium; thereforethepatienthasseverevertigoforaround2weeksuntilthebodycompensatesforthe lack of vestibular input on that side. Most patients will settle over a few days but continuous true vertigo with nystagmus suggests a central lesion. A patient with a deficit of vestibular function due to viral labyrinthitis or neuronitisshouldbeabletoceasevestibularsedativeswithin2weeks;long-termusecangive parkinsonianside-effects,delaycentralcompensationandthusprolongthevertigo. Vestibular rehabilitation by a physiotherapist or audiological scientist can speed up the compensation process,althoughmostpatientswillbeabletodothisthemselveswithtime. Cognitive behavioural therapy through audiological services are of use and rehabilitate patientswell. Theexternalportionofthenoseconsistsoftwonasalbonesattachedtotherestofthefacial skeleton and to the upper and lower lateral cartilages. The blood supply of the nose is derived from branches of both the internal and external carotid arteries. The internal carotid artery supplies the upper nose via the anterior and posterior ethmoidal arteries. The external carotid artery supplies the posterior and inferior portion of the nose via the superior labial artery, greater palatine artery and sphenopalatine artery. ClinicalApproachtothePatientwithaDisorderofthe Nose Examination the anterior part of the nose can be examined using a nasal speculum and light source. CommonDisordersoftheNose Epistaxis Nose bleeds vary in severity from minor to life-threatening. First aid measures should be administered immediately, includingexternal digitalcompression oftheanterior lowerportionof theexternal nose, ice packs and leaning forward. The patient should be asked to avoid swallowing any blood runningposteriorly,asthiscausesnausea. Not infrequently, small, recurrent epistaxes occur and these may require a visit to the emergencyclinicforanexaminationandsimplelocalanaestheticcauterywithasilvernitrate stick. Ifthebleedingcontinuesprofusely,thenresuscitationintheformofintravenousaccess, fluid replacement or blood, and oxygen can be administered. If further intervention is necessary, consideration should be given to intranasal cautery of the bleeding vessel, or intranasal packing using a variety of commercially available nasal packs. Sinusitis Sinusitis is an infection of the paranasal sinuses that is bacterial (mainly Streptococcus pneumoniae and Haemophilus influenzae) or occasionally fungal. It is most commonly associated with an upper respiratory tract infection and can occur with asthma. Management Treatmentforabacterialsinusitisincludesnasaldecongestants,suchasxylometazoline;broadspectrum antibiotics, such as co-amoxiclav because H. Other causes include sinonasal disease, old age, drug therapy and head injury/trauma. Fracturednose People with a fractured nose present with epistaxis, bruising of the eyes and nasal bridge swelling. Thisis painful, can cause nasal obstruction, is fluctuant to touch on the nasal septum, and requires immediatedrainagetopreventdestructionoftheseptalcartilage. Thisconsistsofcartilaginous,ligamentousand muscular tissue that has the primary function of protecting the distal airway. In the larynx, there are two vocal cords that abduct (open) during inspiration and adduct (close)toprotecttheairwayandforvoiceproduction(phonation). Themainnervesupplyof the vocal cords comes from the recurrent laryngeal nerves (branches of the vagus nerve), whichariseintheneck,butontheleftsidepassdownaroundtheaorticarchandthenascend inthetracheo-oesophagealgroovetothelarynx. Normal vocal cords in phonation vibrate between 90 (male) and 180 (female) times per second, giving the voice its pitch or frequency. The remainder of the pharynx and larynx can be inspected with a laryngeal mirror or flexible nasendoscope. CommonDisordersoftheThroat Hoarseness(dysphonia) There are three essential components for voice production: an air source (the lungs); a vibratorysource(thevocalcords);andaresonatingchamber(thepharynxandnasalandoral cavities). Ifsurgeryisneeded,greatcaremustbetakento remain in the superficial layers of the vocal cord in order to prevent deep scarring, which leavesthevoicepermanentlyhoarse. Treatment is to remove the irritation in most cases, but surgery to incise the cords and reduce the oedema will also allow the voice to return to its normalpitch. The voice may be deep, harsh and breathy, indicating a mass on the vocal cord. Medializationof the paralysed cord to allow contact with the opposite cord can return the voice and give a competent larynx. This can be done under local or general anaesthesia, producing an immediateresultwhateverthelong-termprognosisofthechestpathology. Severe stridor may be an indication for either intubation or a tracheostomy(Box30. Amajorproblemwithatracheostomy tubeiscrustingofitsdistalendwithdriedsecretions,andthisarrangementallowstheinner tube to be removed, cleaned and replaced as frequently as required, without disrupting the outertube. Thetracheostomytube itself can alsoproduce problemsdue to compressionof the oesophagus with a cuffed tube and prevention of the larynx from rising during normal swallowing. Tonsillitisandpharyngitis Viral infections of the throat are common and, although many practitioners may be under pressure from the patient to give antibiotics, they should not be used. Fungal infections, usually candidiasis, are uncommon and may indicate an immunocompromisedpatientorundiagnoseddiabetes. Although,clinically,thetonsils have a confluent white exudate, there is often a petechial rash on the soft palate and an accompanyinglymphadenopathy. Thisiscarriedoutunderageneral anaesthetic and current surgical techniques include diathermy dissection, laser excision and coblation(usinganultrasonicdissectingprobe). There is a strong association between snoring and sleep-disorderedbreathing,suchasinobstructivesleepapnoea(seepp. Nasal pathology, such as polyps, can be removed surgically with good results and most patients will benefit from lifestyle changes, such as weight loss. Pharyngealpouch A pharyngeal pouch is a herniation of mucosa through the fibres of the inferior pharyngeal constrictormuscle(cricopharyngeus)(Fig. They can occasionally compress the swelling to allow foodparticlestobepushedbackintotheoesophagus. Theymayalsocomplainthatagurgling sound is heard in the neck following a swallow as liquid and food collect in the pouch. Foreignbodies Foreign bodies in the pharynx can be divided into three general categories: soft food bolus, coins(smooth)andbones(sharp). Radiology can also identify air in the cervical oesophagus, indicating a radiolucent foreign body lying distally. A soft tissue lateral neck radiograph is the investigation of choice to delineatesomeofthefeaturesabove. It is a condition with classic symptoms of an intermittent sensation of a lump in the throat. This is perceived to be in the midlineatthelevelofthecricoidcartilageandisworsewhenswallowingsaliva;indeed,it often disappears when ingesting food or liquids. A contrast swallow will not only show the structures below the pharynx but also assess the swallowingdynamically. It is the cornea and the sclera that give the mechanical strength and shape to the exposed surfaceoftheeye. Theeyelidspreventthe cornea from drying and becoming an irregular surface by distributing the tear film over the surfaceoftheglobewitheachblink. This richly vascularized and innervated mucous membrane stretches from the limbus over the anterior sclera (where it is called the bulbar conjunctiva) and is then reflected on to the undersurface of the upper and lowerlids(thetarsalconjunctiva). The anterior chamber is the space between the cornea and the iris, and is filled with aqueous humour. The outflow of aqueous humour is throughthetrabecularmeshworkandcanalofSchlemmadjacenttothelimbus. The muscles of theiris diaphragm regulate the size of the pupil, thereby controlling the amount of light entering the eye. Bychanging itsshape, itcanalter its refractive power and help to focus objects at different distances from the eye. By the fourth decade of life, this ability to change shape starts to decline and, with time, the lens starts to become less transparent and cataracts begin to develop. Thereareapproximately6millioncones,mainlyconfinedtothemacula,andtheseare responsible for detailed central vision and colour vision. The peripheral retina has around 125million rods that are responsible for peripheral vision. The blood supply to the eye is via the ophthalmic artery; in particular, the central retinal arteryisresponsibleforsupplyingtheinnerretinallayers. ClinicalApproachtothePatientwithaDisorderofthe Eye Historyandexamination A detailed history gives most of the facts needed to make a working diagnosis. Different approaches and instruments (including direct ophthalmoscope, slit lamp with or without Goldman or V lens) are necessary for examination of the lids and anterior and posterior olk segments,aswellasextraocularmovements. The visual acuity of each eye is recorded in two ways: distance visual acuity and nearvisualacuity. The recording is given as an expressionofthelineoflettersthatcanbediscernedataparticulardistance,usually6metres (20feet):forexample6/60,where6equalsthedistanceofthechartfromtheeyeinmetresand 60equalsthedistanceatwhichthelettersubtends5atthenodalpoint. Research conducted using a logarithmic progression in size of letters on a test chart provides the most accurate visual acuity measurement. CommonDisordersoftheEye Refractiveerrors the eye projects a sharp and focused image on to the retina. Refractive errors refer to any abnormalityinthefocusingmechanismoftheeyeandnottoanyopacityinthesystem,suchasa cornealorretinalscar. Therefractionoflightinemmetropic(normal),myopic(short-sighted;negativelenseswill correct) and hypermetropic (long-sighted; positive lenses will correct) eyes is shown in Figure30. Astigmatismisarefractiveerroroftheeyeinwhichthereisadifferentdegreeofrefraction in the different meridians of curvature. Presbyopia is the term used to describe the normal ageing of the lens, which leads to a change in the refractive state of the eye. As the lens ages, it becomes less able to alter its curvatureandthiscausesdifficultywithnearvision,especiallyreading. Management Errors of refraction can be corrected by using spectacles or contact lenses. They may be the only option in some refractive states such as keratoconus, a degenerative disorder of the eye in which structuralchangeswithinthecorneacauseittothinandtotakeonamoreconicalshapethanits normalgradualcurve. The laser either removes corneal tissuecentrallytoflattenthecorneainmyopiaoritremovestissuefromtheperipheralcornea tosteepenitinhypermetropia. As a result, the lacrimal punctumisnotinthecorrectanatomicalpositiontodraintearsandpatientsusuallycomplainof awateryeye. Dacryocystitis Patientswhohaveinflammationofthelacrimalsacusuallypresentwithapainfullumpatthe side of the nose adjacent to the lower lid. This should be treated with oral broad-spectrumantibioticssuchasacephalosporin,andpatientsshouldbewatchedcarefully forsignsofcellulitis. Common underlying causes of blepharitis include meibomian gland dysfunction, seborrhoea and Staphylococcus aureusinfection. Patientscanbeasymptomaticorcomplainofitchy,burningeyesbecauseof tear film instability resulting from meibomian gland dysfunction. A short course of topical chloramphenicolor fusidicacid is useful in chronic cases, but in severe cases or cases where acne rosacea is suspected, oral doxycyclineisused. Most of these patients find the lump, or chalazion, cosmetically unacceptable and requireincisionandcurettage. Commonfeatures in all types include soreness, redness and discharge; in general, the visual acuity is good. Historyshouldincludethespeedofonsetoftheinflammation,thecolourandconsistencyofthe discharge, whether the eye is itchy, and if there has been a recent history of a cold or sore throat. Inthevast majority of patients, it causes a sore or gritty eye in the presence of good vision. Clinicalfeatures Gonococcal conjunctivitis should be suspected when the onset of symptoms is rapid, the discharge is copious, and ocular inflammation includes chemosis (conjunctival oedema) and lid oedema. Gonococci are a cause of conjunctivitis, giving rise to a palpable pre-auricular node. Lessacuteorsubacutepurulentconjunctivitiswithmoderatedischargecanbeattributed to organisms such as Haemophilus influenzae and Streptococcus pneumoniae. Chronic conjunctivitis is usually associated with mild conjunctival injection and scant purulent discharge. Management Prompt treatment with oral and topical penicillin is given in gonococcal conjunctivitis to ensure a reduced rate of corneal perforation. In neonates, the onset of the red eye is typically around 2weeks after birth, whereasgonococcalconjunctivitisoccurswithindaysofbirth. Management Topical erythromycin twice daily is commenced and patients referred to the genitourinary physician. Neonates should be started on topical erythromycin and referred to the paediatrician,astheremaybeassociatedotitismediaorpneumonitis. Inflammation is commonly associated with chemosis, lid oedemaandapalpablepre-auricularlymphnode. Viralconjunctivitis can cause deterioration in visual acuity owing to corneal involvement (focal areas of inflammation). Lubricants, together with a cold compress, can be a soothing element of management for patients. Adhering to strict hygiene and keeping towels separate from those of the rest of the household go a long way towards reducing the spread of the infection. In people with corneal involvement or intense conjunctivalinflammation,topicalsteroidsareindicated. Herpessimplexconjunctivitis Primary ocular herpes simplex conjunctivitis is typically unilateral. Management includes curetting the central portion of the lesion, freezing the centre or completelyexcisingthelesion. Ifthecornealinvolvementissevereortheeyeisveryinflamed, a short course of topical steroids, such as prednisolone 0. It leads to blepharitis with marked conjunctival inflammation, pre-auricular lymphadenopathy and, rarely, secondary infection at thesiteoflousebite. Allergicconjunctivitis There are five main types of allergic conjunctivitis: seasonal, perennial, vernal, atopic and giant papillary. Both seasonal and perennial allergic conjunctivitis are acute allergic conjunctival disorders. These two eye conditions are mediated by mast cells and can be treated easily with cold compresses, eye washes withtear substitutes, andavoidance of allergens. The last three are difficult to treat; theyarechronicandcanbesight-threatening,soshouldbereferredtoanophthalmologist. The main symptoms include itching, redness, soreness, watering and a stringy discharge. Symptoms include severepain, due to exposure of thecorneal nerve endings, lacrimation andinabilitytoopentheeye(blepharospasm). Treatmentconsistsofabroad-spectrumtopicalantibiotic,suchaschloramphenicoldrops or ointment four times a day for 5days. The role of padding is controversial but common practice is to pad the affected eye for 24hours once chloramphenicol ointment has been appliedtotheeye. Examination may show a corneal laceration and a foreign body may also be embeddedinthecornea. Urgent referral to the ophthalmologist is mandatory, ensuring that no drops are instilled into the eye and that a plastic shield is placed over the eye to minimize furtherriskoftrauma. Blunttraumausuallyresultsinperiorbitalbruisingandgrosslidoedema,whichcanmake examination to exclude perforating injury difficult. These patients should be referred to the ophthalmologistforadetailedocularexaminationtoexcludeaperforation,retinaldetachment oratraumatichyphaema(Fig. Commoncausesincludeherpes simplex virus, contact lens-associated infection and blepharitis. Herpessimplexkeratitis Corneal epithelial cells infected with the virus eventually undergo lysis and form an ulcer, which is typically dendritic in shape (see. Keratoconus Keratoconus is an eye condition in which the normally round, dome-shaped cornea progressively thins and causes a cone-shaped bulge to develop. Keratoconus affects up to 1 in 1000 people and is more common in individuals of Asianheritage. Management In the early stages, spectacles or soft contact lenses may be used to correct vision.
While reforms are certainly called for treatment 5th metacarpal fracture buy discount pristiq 50mg on-line, current efforts pose a serious risk to judicial independence in the country symptoms gout discount pristiq 100mg without prescription. In 2016 symptoms 11dpo generic pristiq 50mg on-line, members of the three branches of government medicine 02 50 mg pristiq amex, as well as civil society groups and other stakeholders symptoms endometriosis order 100 mg pristiq overnight delivery, discussed proposals during a "National Justice Summit treatment rheumatoid arthritis buy pristiq 100 mg without prescription. In 2017 treatment research institute pristiq 100mg cheap, Congress created a commission to oversee implementation of the recommendations medicine 95a generic 100 mg pristiq with mastercard. The commission has broad powers, including "controlling" the appointment of new judges and carrying out "all other actions necessary" to implement the recommendations. A Supreme Electoral Tribunal decision on whether President Morales could register as a candidate for the 2019 presidential election remained pending at time of writing. Due Process and Prison Conditions Around 70 percent of all Bolivians in detention have not been convicted of a crime. Extended pretrial detention and trial delays overcrowd prisons and lead to poor and inhumane conditions. By mid-2018, more than 16,000 inmates were packed into prisons built to hold a maximum of around 5,000. In March 2018, seven prisoners died during a police operation in Palmasola prison in Santa Cruz. The government said the operation sought to recover control of the prison from criminal organizations. Presidential decrees adopted between 2012 and 2018 allow the president to reduce the sentences of those convicted of minor crimes and drop charges against those held in pretrial detention for minor crimes. Official figures reveal that more than 5,000 people have benefited from such decrees. International human rights law, however, prohibits such retroactive application of changes to criminal law, unless doing so is beneficial to the defendant. In May 2015, Jorge "Tuto" Quiroga, former president of Bolivia and current opposition leader, was charged with "anti-economic conduct. In May 2017, President Morales signed a bill that authorizes the building of a highway in the Isiboro Secure National Park and Indigenous Territory. The law is based on a 2012 consultation with local indigenous groups, which some rights groups say was not fully free or fair. Human Rights Defenders Human rights defenders continue to face harassment, including from government officials, which undermines their ability to work independently. A law and decree that President Morales signed in 2013 grants the government broad powers to dissolve civil society organizations. Bolivian officials have repeatedly accused rights groups of engaging in an international conspiracy against the government, but have failed to present evidence to support such claims. Gender-Based Violence and Reproductive Rights Women and girls in Bolivia remain at high risk of gender-based violence, despite a 2013 law that sets forth comprehensive measures to prevent and prosecute violence against women. The law created the crime of "femicide" (the killing of a woman in certain circumstances, including of domestic violence) and called for the establishment of shelters for women as well as special prosecutors and courts for gender-based crimes. Women and girls face numerous obstacles to accessing sexual and reproductive health services, including contraceptives. Under Bolivian law, abortion is not a crime when the pregnancy is due to rape or if the procedure is necessary to protect the life or health of a pregnant woman or girl. In December 2017, the Plurinational Assembly passed government-sponsored criminal reform that would significantly eased abortion restrictions. But, in response to protests, the assembly abrogated the bill in January 2018, before it took force. It would have allowed women to end pregnancies in a range of circumstances, in- Freedom of Expression While public debate is robust, the Morales administration periodically lashes out at journalists, accusing them, without presenting evidence, of publishing lies and politically motivated distortions. The government has repeatedly accused media of participating in an international conspiracy against Bolivia and the president. Bolivia lacks transparent criteria for using government funds to purchase media advertisements-an important source of media revenue-and some media outlets have accused the government of discriminating against those who criticize government officials by withholding advertising from them. Bosnia and Herzegovina Bosnia and Herzegovina made limited progress in 2018 towards addressing long-standing human rights problems. Members of national minorities were ineligible to stand for the presidency in the 2018 general elections because of the ongoing failure to amend discriminatory provisions of the constitution. Authorities did not provide basic support to thousands of asylum seekers and migrants who arrived in 2018. Child Labor In February 2018, the Constitutional Court abrogated a provision in a 2014 law that had allowed children as young as 10 to work in activities that are not deemed "dangerous" or "unhealthy. Political disagreements mean the city has not held local elections since 2008, disenfranchising its voters. A survey conducted in April 2018 by the United Nations Development Programme showed Roma in Bosnia and Herzegovina continue to face many difficulties accessing and enjoying, health care, education, housing, and employment, notwithstanding some improvements in living standards. Sexual Orientation and Gender Identity In 2016, the Plurinational Assembly passed a bill that allows people to revise the gender listed on their identification documents without prior judicial approval. However, in November 2017, the Constitutional Court ruled that revision of gender did not grant the right to marry a person of the same biological sex. Also in April, the Inter-American Commission on Human Rights accepted a case concerning the April 2009 killing of two Hungarians (one of Bolivian birth) and an Irishman, whom the government alleged were mercenaries involved in a separatist plot. President Morales tweeted that admitting the case meant that the commission "was a defender of terrorism and separatism. Asylum Seekers and Internally Displaced Persons the numbers of asylum seekers and migrants entering the country increased significantly during the year. The state did not provide adequate shelter, food, and access to medical assistance to the new arrivals, particularly in Velika Kladusa and Bihac municipalities. In November 2018 there were only two state-managed centers for migrants and refugees-an open asylum center with capacity of about 154, and an open refugee reception center with capacity of around 290-and two temporary accommodation centers for migrants set up with support of international organizations. The lack of accommodation and services forced thousands to live in the streets, abandoned buildings, or tents. The lack of official accommodation means that many would-be asylum seekers cannot register a place of residence upon arrival, a requirement to apply for asylum. This leaves many without access to asylum procedures even after they register their intention to apply. Among the 2018 arrivals, over 19, 900 asylum seekers expressed intention to apply for asylum, but only 1,314 applied. Twenty-three years after the end of the war in Bosnia, only 42 percent of Bosnian refugees have returned to Bosnia, according to the Ministry for Human Rights and Refugees, and 91,813 remained internally displaced at the end of June 2018, many still living in 156 collective centers. At time of writing, 737 homes for internally displaced had been built under the Regional Housing Programme. A plan to build housing for displaced people living in 121 collective centers by 2020 under a Council of Europe Development Bank-funded project had started but was moving slowly in most municipalities. A revised National War Crimes Processing Strategy has been waiting approval by the Council of Ministers since February 2018. The revised strategy aims to improve the process of determining which cases merit handling by the State Court War Crimes Chamber and prosecutor, and which can be dealt with in entity, district, and cantonal courts. There were 114 cases for war crimes before the State Court involving 296 defendants as of September 2018. Between January and September 2018, the court delivered 29 verdicts, 14 convictions, 12 acquittals, and three partial acquittals. The court delivered seven verdicts for conflict-related sexual violence, five of which were convictions. Between January and September 2018, the Supreme Court of Republika Srpska, which tries war crimes cases in that entity, received seven war crime cases, four of which resulted in convictions and three of which were being processed at time of writing. Statistics for cantonal courts in the federation were not available at time of writing. In January 2018, the State Court confirmed a genocide indictment against former Bosnian Serb Interior Minister Tomislav Kovac. He is accused of controlling the police forces involved in capturing, detaining, and executing up to 8,000 Bosniak men in Srebrenica in 1995. Human Rights Defenders and Civil Society In 2018, civil society groups reported intensified state efforts to discourage public protests by issuing fines for public disorder, making it increasingly difficult and slow to obtain necessary permits, restricting protests to specific and less central areas, and over-policing peaceful events. In a notable development, Republika Srpska amended its criminal law to include an offence of public incitement to violence and hatred based on sex, sexual orientation, and gender identity. Key International Actors In May 2018, Council of Europe (CoE) Commissioner for Human Rights Dunja Mijatovic urged the minister for human rights and refugees and the minister for security to address the migration crisis in a way that is compliant with human rights. In their August 2018 concluding observations of the periodic report of Bosnia and Herzegovina, the United Nations Committee on the Elimination of Racial Discrimination called on Bosnian authorities to include in its criminal code all grounds for discrimination, ensure that local laws enable equal rights for all, and end "two schools under one roof," the practice of ethnic-based segregation within a single school. Freedom of Media Attacks on journalists and freedom of media continued at high rate in 2018. He was hospitalized, and at time of writing the attack was being investigated by police as an attempted murder. In response to the attack, the public and other journalists organized protest walks demanding better safety and protection standards for journalists. Political violence and threats against journalists marred the presidential contest. Domestic violence remains widespread; thousands of cases each year are not properly investigated. Tens of thousands of Venezuelans poured into Brazil in 2018 fleeing repression, hunger, and inadequate medical care. Brazil has kept its borders open, but there have been several serious xenophobic attacks against Venezuelans. Many rural Brazilians are exposed to pesticides sprayed near their homes, schools, and workplaces, and they fear reprisals if they report poisonings. Public Security and Police Conduct A large-scale study by criminologists and journalists estimates that prosecutors file charges in only two out of every ten homicides. Abuses by police, including extrajudicial executions, contribute to a cycle of violence that undermines public security and endangers the lives of police officers and civilians. The federal government has failed to publish a yearly report about killings by and of police officers, as ordered by the Inter-American Court of Human Rights in a 2017 ruling. Data compiled by the nonprofit Brazilian Forum on Public Security from official sources show that 367 on- and off-duty police officers were killed in 2017, the latest available information. Police officers, including off-duty officers, killed 5,144 people in 2017, 20 percent more than in 2016. While some police killings are in self-defense, research by Human Rights Watch and other organizations shows that some are extrajudicial executions. A 2017 law moved trials of members of the armed forces accused of unlawful killings of civilians from civilian to military courts. The law also moved trials of military police-the state police force that patrols the streets in Brazil-accused of torture and other crimes to military courts, although homicides by them remain in civilian jurisdiction. This means that the armed forces and military police investigate their own members who are accused of crimes. Under international norms, extrajudicial executions and other grave human rights violations by police and the military must be investigated by civilian authorities and tried in civilian courts. At time of writing, neither armed forces investigators nor federal military prosecutors had interviewed any civilian witnesses. Yet from March to October, homicides went up by 2 percent in Rio State, while police killings increased by 44 percent, compared to the same period in 2017. Among the Rio homicide victims were councilwoman and human rights defender Marielle Franco and her driver, Anderson Gomes, gunned down in a professional killing in March. Fewer than 15 percent of inmates have access to educational or work opportunities, and health services are often deficient. In February, the Supreme Court ruled that pregnant women, mothers of children under 13, and mothers of children and adults with disabilities who are in pretrial detention for non-violent crimes should instead await trial under house arrest, except for "very exceptional cases. Judges made widespread use of a "very exceptional cases" exception to retain women in jail. Many people awaiting trial are routinely held with convicted prisoners, in violation of international standards and Brazilian law. The National Council of Justice ordered that by May 2016 all detainees should be taken, within 24 hours of arrest, to a hearing to determine if they should be in preventive detention or set free pending trial. But more than two years later, many jurisdictions outside state capitals still do not hold such "custody hearings. At custody hearings, judges can detect police abuse, yet some do not ask detainees about their treatment. In most cases, police officers are present during the hearing, which can be intimidating. Still, about 5 percent of detainees report abuse during the hearings, according to the National Council of Justice. Several studies have shown that their allegations are often not properly investigated. At time of writing, Congress was examining a bill to make custody hearings mandatory countrywide. But the bill would allow some to be held via videoconference with people in their places of detention, which would make the hearings far less useful as a genuine opportunity to discover allegations of police abuse. Prison Conditions, Torture, and Ill-Treatment of Detainees In June 2016, more than 726,000 adults were behind bars in facilities built to hold half that number, Ministry of Justice data show. Overcrowding and understaffing make it impossible for prison authorities to maintain control within many prisons, leaving detainees vulnerable to violence and recruitment into gangs. Investigations by the National Mechanism for the Prevention and Combatting of Torture and Human Rights Watch have revealed scores of cases of mistreatment in various states. Military police have abused desacato to quell criticism, for example, detaining people participating in protests, saying they disrespected officers. State disciplinary codes and the military criminal code subject officers to expulsion from the force and prison sentences for offenses, such as criticizing a superior officer or a government decision. Official data show that 23 shelters that housed women and children in desperate need closed in 2017 due to budget cuts. Each year, police do not properly investigate thousands of domestic violence cases, with the result that they are never prosecuted. In 2017, the last year for which data is available, 4,539 women were killed in Brazil, the Brazilian Forum on Public Security reports. Police registered 1,133 as femicides, defined under Brazilian law as the killing of a woman "on account of being persons of the female sex. Women and girls who have clandestine abortions not only risk injury and death but face up to three years in prison, while people convicted of performing unlawful abortions face up to four years. In August, the Supreme Court held a two-day hearing on a pending petition to decriminalize abortion in the first 12 weeks of pregnancy. An outbreak of the Zika virus in 2015-2016 caused particular harm to women and girls. When a pregnant woman is infected, Zika can cause complications in fetal development, including of the brain. Ministry of Health data from June showed that two-thirds of children born with Zika syndrome had not received the specialized early stimulation that is crucial for their development. Freedom of Expression More than 140 reporters covering the elections were harassed, threatened, and in some cases physically attacked, the Brazilian Association of Investigative Journalism (Abraji) found. After winning the election, Bolsonaro said he would withdraw state advertising from news media that are "unworthy. The ruling comes as Bolsonaro and his allies push a bill that would prohibit teachers from promoting their own opinions in the classroom or using the terms "gender" or "sexual orientation," and would order that sex and religious education be framed around "family values. A fourth justice maintained that punishing "disrespect" violates freedom of expression. The Brazilian Bar Association has petitioned the Supreme Court to rule the desacato provision unconstitutional. A person stripped of legal capacity can only leave an institution with the consent of their guardian, which constitutes unlawful deprivation of liberty according to the Convention on the Rights of People with Disabilities, which Brazil has ratified. In June, the Senate approved a bill that recognizes a right to legal capacity for some adults with disabilities. The bill does not establish universal legal capacity or a system that allows all people with disabilities access to supported decisionmaking. Migrants, Refugees, and Asylum Seekers Thousands of Venezuelans have crossed the border into Brazil fleeing hunger, lack of basic health care, and persecution. The government has been slow to integrate them into society; most children in shelters do not go to school, and many Venezuelans still lack legal papers. By November, more than 3,100 Venezuelans had benefited from a federal program that relocates them to other states. In March, a mob expelled Venezuelans from an improvised shelter in Roraima, the Brazilian state that borders Venezuela, and burned their belongings; in August, after another attack, a mob pushed about 1,200 Venezuelans back across the border while police looked on, making no arrests; and in September, several Brazilians lynched a Venezuelan whom they accused of a killing. In March, the Supreme Court ruled that the government can no longer require transgender people who want their name and gender marker on identification documents changed to undergo medical procedures or subject their decisions to judicial review. Brazilian media reported about dozens of cases of threats and attacks against lesbian, gay, bisexual, and transgender people during the presidential campaign, many of them allegedly by Bolsonaro supporters. In 2017, 71 people involved in land conflicts died violently, the highest number since 2003, the Pastoral Land Commission of the Catholic Church reported. In March, then-President Temer issued three decrees implementing a 2017 federal law that would grant titles to people occupying land illegally. Environmental and landless peasant organizations argue that the law would benefit large landowners and illegal loggers.
Human albumin solutions are generally considered to be inappropriate fluids for acute volumereplacementorforthetreatmentofshockbecausetheyarenomoreeffectiveinthese situations than synthetic colloid solutions medicine you take at first sign of cold 50 mg pristiq with mastercard, such as polygelatins (Gelofusine) or hydroxyethyl starch (Haemaccel) administering medications 7th edition ebook purchase pristiq 50 mg amex. However treatment quadricep strain discount pristiq 100mg otc, albumin solutions are indicated for treatment of acute severe hypoalbuminaemia and as the replacement fluid for plasma exchange medications 1040 discount 50 mg pristiq with mastercard. The 20% albumin solution is particularly useful for patients with nephrotic syndrome or liver disease who are fluid-overloaded and resistant to diuretics in treatment 2 purchase 100 mg pristiq. Albumin solutions should not be used to treat patientswithmalnutritionorchronicrenalorliverdiseasewhohavealowserumalbumin medicine prices pristiq 50 mg online. Specificimmunoglobulins these are obtained from donors with high titres of antibodies medicine rap song purchase pristiq 100mg fast delivery. It relies on the regenerative potential of transfused haemopoietic stem cells to repopulate the marrow niche that has been rendered temporarily or permanently hypoplastic by chemotherapy with or withoutadditionalradiotherapy treatment 32 for bad breath cheap pristiq 50 mg otc. Allogeneic transplantation has been successfully used in a number of haemopoietic malignancies: most commonly, acute leukaemias. The engraftment of the donor immune system, with antitumour activity(graft-versus-tumour),isprimarilyresponsiblefortheincreasedeffectivenessofthis approach. Hepatitis E virus in blood components: a prevalenceandtransmissionstudyinsoutheastEngland. TheWhiteCell the five types of leucocytes found in peripheral blood are: neutrophils, eosinophils and basophils (which are all called granulocytes), and lymphocytes and monocytes (see also pp. Neutrophils the earliest morphologically identifiable precursors of neutrophils in the bone marrow are myeloblasts,whicharelargecellsconstitutingupto3%ofthenucleatedcellsinthemarrow. Promyelocytes are similar to myeloblasts but have some primary cytoplasmic granules,containingenzymessuchasmyeloperoxidase. Myelocytesaresmallercellswithout nucleoli but with more abundant cytoplasm and both primary and secondary granules. Peripheral blood neutrophils are equally distributed into a circulating pool and a marginating pool lying along the endothelium of blood vessels. Function the prime function of neutrophils is to ingest and kill bacteria, fungi and damaged cells. Recognitionof foreign or dead material is aided by the coating of particles with immunoglobulin and complement(opsonization),asneutrophilshaveFcandC3breceptors(seepp. The materialisingestedintovacuoles,whereitissubjectedtoenzymicdestruction;thisiseither oxygen-dependent, with the generation of hydrogen peroxide (myeloperoxidase), or oxygenindependent(lysosomalenzymesandlactoferrin). This may also be seen in pregnancy, during exercise and after corticosteroid administration (Box 16. With any tissue necrosis, there is a release of varioussolublefactors,causingaleucocytosis. Aleucoerythroblasticbloodfilm (an overproduction of white cells, with many immature cellsandnucleatedredcells)mayoccurinmanytypesofsevereacuteillness. Chemotherapy and radiotherapy predictably produce neutropenia;manyotherdrugshavebeenknown toproduceanidiosyncraticcytopeniaanda drugcauseshouldalwaysbeconsidered. Management Antibiotics should be given as necessary to patients with acute severe neutropenia (see pp. If the neutropenia seems likely to have been caused by a drug, all current drug therapy shouldbestopped. Eosinophils Eosinophils are slightly larger than neutrophils and are characterized by a nucleus, usually withtwolobes,andlargecytoplasmicgranulesthatstaindeeplyred. BindingofIgEcauses the cells to degranulate and release histamine and other contents involved in acute hypersensitivityreactions(seep. Monocytes are precursors of tissue macrophages and dendritic cells; they spend only a few hoursinthebloodbutcancontinuetoproliferateinthetissuesformanyyears. Circulating lymphocytes are small cells, a little larger than red cells, withadark-stainingcentralnucleus. Haemostasis Haemostasis is a complex process that depends on interactions between the vessel wall, leucocytes, platelets, coagulation and fibrinolytic mechanisms. Vesselwall the vessel wall is lined by endothelium, which, in normal conditions, prevents platelet adhesionandthrombusformation. Within secondsofadhesiontothevesselwall,plateletsbegintoundergoashapechange,fromadisc to a sphere, spread along the subendothelium and release the contents of their cytoplasmic granules. Plateletaggregation Asfibrinogenisadimer,itcanformadirectbridgebetweenplateletsandsobindsplatelets into activated aggregates (platelet aggregation;. A self-perpetuating cycle of events is set up, leading to formation of a platelet plugatthesiteoftheinjury. The presence of thrombin encourages fusion of platelets, and fibrin formation reinforces the stability of the platelet plug. Coagulationandfibrinolysis Coagulation involves a series of enzymatic reactions that lead to the conversion of soluble plasmafibrinogentofibrin-basedclot(Fig. ActivatedproteinC this is generated from its vitamin K-dependent precursor, protein C, by thrombin; thrombin activation of protein C is greatly enhanced when thrombin is bound to thrombomodulin on endothelial cells. Otherinhibitors Other natural inhibitors of coagulation include 2-macroglobulin, 1-antitrypsin and 2antiplasmin. Fibrinolysis Fibrinolysis is a normal haemostatic response that helps to restore vessel patency after vasculardamage. Some plasminogen activation may also be promoted by urokinase, produced in the kidneys. Its presence in the plasma indicates that the coagulationmechanismhasbeenactivated. However, little plasminogen activation occurs in the absence of polymerized fibrin, as fibrin also has a specific binding site for plasminogen activators,whereasfibrinogendoesnot(Fig. Investigationofbleedingdisorders Although the precise diagnosis of a bleeding disorder will depend onlaboratory tests, much informationisobtainedfromthehistoryandphysicalexamination. Supportive evidence for a generalized haemostatic defect includes bleeding from multiple sites,spontaneousbleeding,andexcessivebleedingafterinjury. Severe inherited defects usually becomeapparentininfancy,sometimesatthetimeofbirthwithprolongedbleedingfromthe umbilical cord, while mild inherited defects may only come to attention later in life: for example,withexcessivebleedingaftersurgery,childbirth,dentalextractionsortrauma. Some defects are revealed by routine coagulation screens that are performed before surgical procedures. Purpuraincludesbothpetechiae,smallskinhaemorrhagesvarying frompinpointsizetoafewmillimetresindiameterandwhichdonotblanchonpressure,and ecchymoses, larger areas of bleeding into the skin. Coagulationtests these are performed using blood collected into citrate, which neutralizes calcium ions and preventsclotting. Bleeding from mucous membranes sometimes occurs but the bleeding is rarely severe. Dilatation of capillaries and small arterioles produces characteristic small, red spots that blanch on pressure in the skin and mucous membranes, particularly the nose and gastrointestinal tract. Recurrent epistaxis and chronic gastrointestinal bleeding are the major problems that cause chronic iron deficiency anaemia. Vascular malformations also occur in pulmonary, hepatic cerebral and spinal vasculature. Purpuraduetoinfections this is mainly caused by damage to the vascular endothelium. Episodesofinexplicablebleedingorbruising Thesemay representabuse, eitherself-inflicted or causedby others. PlateletDisorders Bleeding due to thrombocytopenia or abnormal platelet function is characterized by purpura and bleeding from mucous membranes. The underlying causemayberevealedbyhistoryandexaminationbutabonemarrowexaminationwillshow whether the numbers of megakaryocytes are reduced, normal or increased, and will provide essential information on morphology. The antibody-coated platelets are removed following binding to Fc receptors on macrophages. Clinicalfeatures Major haemorrhage is rare and is seen only in patients with severe thrombocytopenia. Normal or increased numbers of megakaryocytes are found in the bone marrow (if examination is performed), which is otherwisenormal. Thedetectionofplateletautoantibodiesisnotessentialforconfirmationof the diagnosis, which often depends on exclusion of other causes of excessive destruction of platelets. Where treatment is necessary on clinical grounds, corticosteroids, intravenous immunoglobulin. IgG is effective in more than 80% of children and raises the count more rapidly than steroids. Patients with even lower platelet counts may not require treatmentunlesstheyhavespontaneousbruisingorbleeding. Approximately66%willrespondto prednisolone but relapse is common when the dose is reduced. Otherimmunethrombocytopenias Drugs Drugscauseimmunethrombocytopeniabythesamemechanismsasthosedescribedfordruginduced immune haemolytic anaemia (see p. The same drugs can be responsible for immunehaemolyticanaemia,thrombocytopeniaorneutropeniaindifferentpatients. There is a characteristic symptom complex of florid purpura, fever, fluctuating cerebral dysfunction and microangiopathichaemolyticanaemiawithredcellfragmentation,oftenaccompaniedbyacute kidney injury. Pulsed intravenous methylprednisolone is given acutely; increasingly, rituximabisalsoaprimarytreatmentofchoice. Caplacizumab is a single-variable-domain immunoglobulin directed to the A1 region of the von Willebrand factor. Bleeding in renal disease is multifactorial, although platelet dysfunction is a major component. Essential thrombocythaemia, a myeloproliferative neoplasm that is described on page 550, and other myeloproliferative conditions such as polycythaemia vera, myelofibrosis and chronicmyeloidleukaemiamayalsobeassociatedwithahighplateletcount. Inmyeloproliferativediseases,theprimaryriskisthrombosisandspecificaction is often taken to reduce the platelet count, usually with hydroxycarbamide (hydroxyurea). InheritedCoagulationDisorders Inherited coagulation disorders are uncommon and usually involve deficiency of one factor only. In inherited coagulation disorders, deficiencies of all factors have been described. Ifafemalecarrierhasason,hehasa50%chanceofhavinghaemophilia;a daughter has a 50% chance of being a carrier. There is a high mutation rate, one-third of cases being apparently sporadic withnofamilyhistoryofhaemophilia. The most common causes of death in people with haemophilia are cancer and heart disease, as for the general population, rather than bleeding, although cerebral haemorrhage is much more frequent than in the general population. Recombinant products are the treatment of choice but economic constraintsoftenlimitavailability,particularlyindevelopingcountries. It avoids the complications associated with blood products and is useful for treatingandpreventingbleedinginmildhaemophilia. In those recently identified as having developed an inhibitor, the long-term aim is to eradicate the inhibitory antibody. This is done using immune tolerance induction strategies, sometimeswithadditionalimmunosuppression. Management Management depends on the severity of the condition and may be similar to that of mild haemophilia,includingtheuseofdesmopressinwherepossible. NewbornbabieshavelowlevelsofvitaminKandthismaycauseminorbleedinginthefirst week of life (classical haemorrhagic disease of the newborn). Suchsystemicactivationleadstowidespreadgenerationoffibrinand deposition in blood vessels, leading to thrombosis and multiorgan failure. These further contribute to the coagulation defect by inhibiting fibrin polymerization. The consequences of these changes are a mixture of initial thrombosis, followed by a bleeding tendency due to consumption of coagulation factors and dysregulatedfibrinolyticactivation. Bleeding may occur from the mouth, nose and venepuncture sites, andtheremaybewidespreadecchymoses. Transfusionof blood components on the basis of coagulation tests alone is not required. Inthosecaseswithadominantthromboticcomponent,thecautioususe of unfractionated heparin should be considered. Longer-term therapy is to eliminate the autoantibodyusingimmunosuppression,suchassteroids,cyclophosphamideorrituximab. Thrombosis A thrombus is defined as a solid mass formed in the circulation from the constituents of the bloodduringlife. Arterialthrombosis this usually occurs in association with atheroma, which tends to form at areas of turbulent blood flow, such as the bifurcation of arteries. Thisresultsincomplete occlusion of the vessel or embolization thatproduces distal obstruction. Arterial thrombi may also form in the heart, as mural thrombi in the left ventricle after myocardialinfarction,intheleftatriuminmitralvalvedisease,oronthesurfacesofprosthetic valves. Venousthrombosis Unlike arterial thrombosis, venous thrombosis often occurs in normal vessels. The propagating thrombus is formed of fibrin and platelets, and is particularly liable to embolize. Chronic venous obstruction following thrombosis in the deep veins of the leg frequently results in a permanently swollen limb and may lead to ulceration (post-phlebitic syndrome). Venousthrombosismayoccur with changes in blood cells, such as polycythaemia and thrombocythaemia, and with coagulationabnormalities(thrombophilia;seebelow). Factor V Leiden acts synergistically with other acquired thrombosis risk factors: for example, in those who are taking oral contraceptive pills or are pregnant. Thrombosis risk rises 35-fold in those on a combined oral contraceptive pill, although the absolute risk for thrombosisremainsatsignificantlybelow0. Prothrombinvariant A mutation in the 3 untranslated region of the prothrombin gene has been described (G20210A). Recurrent thrombotic episodes occur, starting at a young age in the inherited variety. Patients may be relatively resistant to heparin, as antithrombinisrequiredforitsaction. ProteinCandSdeficiencies these autosomal dominant conditions result in an increased riskof venous thrombosis, often before the age of 40years. Homozygous protein C or S deficiency causes neonatal purpura fulminans, which is fatal without immediate replacement therapy. Homocysteine When elevated, this amino acid is associated with both arterial thrombosis and venous thromboembolism. Preventionandtreatmentofarterialthrombosis Attempts to prevent or reduce arterial thrombosis are directed mainly at minimizing factors predisposingtoatherosclerosis. Antiplateletdrugs Platelet activation at the site of vascular damage is crucial to the development of arterial thrombosis,andthiscanbealteredbythefollowingdrugs(Box16. The indications for and results of antiplatelet therapy are discussed in the appropriate sections(seep. Thrombolytictherapy Streptokinase Streptokinase is a purified fraction of the filtrate obtained from cultures of haemolytic streptococci. It forms a complex with plasminogen, resulting in a conformational change, whichactivatesotherplasminogenmoleculestoformplasmin. Streptokinaseisantigenicand the development of streptococcal antibodies precludes repeated use. Theyare relatively fibrinspecific, and have relatively little systemic activity and short half-lives (around 5min). The bleeding complications observed are similar in severity and frequency to those seen with streptokinase,suggestingthatfibrinspecificitydoesnotconferprotectionagainsthaemorrhage. Indications the use of thrombolytic therapy in myocardial infarction is discussed on page 1003. The combination of aspirin with thrombolytic therapy produces better results than thrombolytic therapy alone. Treatment should not be given to patients who have had recent bleeding, uncontrolled hypertension or a haemorrhagic stroke, or surgery or other invasive procedures within the previous10days. The incidence is also high in patients confined to bed following trauma, myocardial infarction or other illnesses. Unfortunately the diagnosis can be difficulttomakebecausepatientsonheparinareoftenverysickandmaybethrombocytopenic formanyotherreasons. A long-acting version, idraparinux, is also available and only needs to be given weekly.
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Repeated measurements of lung function are useful for assessing the progressionofdiseaseinindividualpatients treatment depression purchase 100mg pristiq mastercard. Spirometry the patient takes a maximum inspiration followed by a forced expiration (for as long as possible)intothespirometer denivit intensive treatment buy pristiq 50mg free shipping. Regular measurements of peak flow rates on waking symptoms pulmonary embolism discount pristiq 50mg line, during the afternoon medicine woman cast discount pristiq 100 mg without prescription, and before going to bed demonstrate the wide diurnal variations in airflow limitation that characterize asthma and allowobjectiveassessmentofresponsetotreatment(Fig symptoms 8 days after iui discount 100mg pristiq visa. Asairis exhaled symptoms 0f heart attack order pristiq 50mg free shipping, lung volume reduces and the flow rate becomes dependent on the resistance of smallerairways treatment 100 blocked carotid artery purchase pristiq 50mg overnight delivery. Under these circumstances treatment of pneumonia discount pristiq 100mg with amex, the thoracic gas volume can be measured more accurately using a body plethysmograph (see above). The difference between measurements made by these two methods shows the extent of noncommunicatingairspacewithinthelungs. Although relatively non-specific, gas transfer is particularly useful in the detection and monitoring of diseases affecting the lung parenchyma. Measurement of the partial pressures of oxygen and carbon dioxide in arterial blood is essentialinmanagingrespiratoryfailureandsevereasthma,whenrepeatedmeasurementsare oftenthebestguidetotherapy. Peripheraloxygensaturation(Sp O2)canbecontinuouslymeasuredusinganoximeterwith either ear or finger probes. Pulse oximetry has become an essential part of the routine monitoringofpatientsinhospitalandclinics. Other blood investigations sometimes required include 1-antitrypsin levels, Aspergillus antibodies, viral and mycoplasma serology, autoantibody profiles and specific IgE measurements. More sophisticated cardiopulmonary exercise tests are useful in investigating unexplained breathlessness. Large amounts of fluid can be aspiratedthroughalarge-boreneedletohelprelieveextremebreathlessness. Intercostaldrainage Thisiscarried outwhenlargeeffusions arepresent,producingseverebreathlessness,orfor drainage of an empyema (Box 24. Mediastinoscopy Mediastinoscopy is used in the diagnosis of mediastinal masses and in the staging of nodal disease in carcinoma of the bronchus. An incision is made just above the sternum and a mediastinoscopeinsertedbybluntdissection. Under local anaesthesia and sedation, the central airways can be visualized down to subsegmental level and biopsies taken for histology. Diffuseinflammatoryandinfectivelungprocessesmaybesampled by bronchoalveolar lavage and transbronchial biopsy. The yield is best in sarcoidosis, lymphangitis carcinomatosa and hypersensitivity pneumonitis. Skin-pricktests Allergen solutions are placed on the skin (usually the volar surface of the forearm) and the epidermis is broken using a 1mm tipped lancet. Awealofatleast3mmdiameterisregardedaspositive,provided that the control test is negative. Skin tests are not affected by bronchodilators or corticosteroids but antihistamines shouldbediscontinuedatleast48hoursbeforetesting. Itcausesreleaseofenzymesfromneutrophilgranulocytesandmacrophagesthat are capable of destroying elastin and leading to lung damage. Pulmonary epithelial permeability increases, even in symptomless cigarette smokers, and correlates with the concentration of carboxyhaemoglobin in blood. Sputumproductionandairflowlimitation increase with daily cigarette consumption, and effort tolerance decreases. Smoking 20 cigarettes daily for 20years increases the lifetime risk of lung cancer by about 10 times comparedtoalifelongnon-smoker. Nationalcampaigns,bansonadvertisingandasubstantialincreaseinthecostof cigarettes are the best ways of achieving this at the population level. Meanwhile, active encouragement to stop smoking remains a useful approach for individuals. Smokers who want to stop should have access to smoking cessation clinics to provide behavioural support. Bothshouldbeusedonlyinsmokerswhocommittoatargetstopdate, and the initial prescription should be for 2weeks beyond the target stop date. Varenicline is an oral partial agonist on the 42 subtype of the nicotinic acetylcholine receptor. It stimulates the nicotine receptor and reduces withdrawal symptoms and also the cravingforcigarettes. Electronic cigarettes (battery-operated vaporizer)areausefulalternativeforex-smokerswhomissthephysicalprocessofhandling cigarettes and inhaling nicotine. While E-cigarettes are not harmless, they are much less harmfulthanordinarycigarettes. Worldwideburdenofdiseasefromexposure to second-hand smoke: a retrospective analysis of data from 192 countries. DiseasesoftheUpperRespiratoryTract Rhinitis Thecommoncold(acutecoryza) this highly infectious illness (see p. Infectivity from close personal contact (nasal mucus on hands) or droplets is high in the early stages of the infection, and spread is facilitated by overcrowding and poor ventilation. The clinical features are tiredness, slight pyrexia, malaise, and a sore nose and pharynx. Sneezing and profuse, watery nasaldischarge are followed by thick mucopurulentsecretions thatmaypersistforuptoaweek. Nasalirritation,sneezingandwateryrhinorrhoeaoccur,butmanyalsosufferfromitchingof the eyes and soft palate, and occasionally even itching of the ears because of the common innervationofthepharyngealmucosaandtheear. Perennialrhinitisis most frequent in thesecondandthird decades, decreasingwith age, andcanbe dividedinto fourmaintypes. Perennialallergicrhinitis the most common cause is allergy to the faecal particles of the house-dust mite, Dermatophagoidespteronyssinus or D. Thenextmostcommonallergenscomefromdomesticpets(especiallycats)andareproteins derived from urine or saliva spread over the surface of the animal, as well as skin protein. Perennialnon-allergicrhinitiswitheosinophilia No extrinsic allergic cause can be identified, either from the history or on skin testing, but eosinophilicgranulocytesarepresentinnasalsecretions. Vasomotorrhinitis these patients with perennial rhinitis have no demonstrable allergy or nasal eosinophilia. Waterysecretionsandnasalcongestionaretriggeredby,forexample,coldair,smoke,perfume or newsprint, possibly because of an imbalance of the autonomic nerves controlling the erectiletissue(sinusoids)inthenasalmucosa. They contain mast cells,eosinophilsandmononuclearcellsinlargenumbersandcausenasalobstruction,lossof smell and taste, and mouth breathing, but rarely sneezing, since the mucosa of the polyp is largelydenervated. Pathogenesisofrhinitis Sneezing, increased secretion and changes in mucosal blood flow are mediated both by efferent nerve fibres and by released mediators (see p. Sympathetic fibres maintain tonic contraction of blood vessels, keepingthesinusoidsofthenosepartiallyconstrictedandaidingnasalpatency. These latter symptoms are driven by increased epithelial permeability, mostly due to histamine. Additionally, allergens are presented to T cells via antigen-presenting cells (dendritic cells). Investigationsanddiagnosis the allergic factors causing rhinitis can usually be identified from the history. However, if there is a compatible clinical history, it is more likelytoberelevant. Allergen-specificIgEantibodiescanbemeasuredinbloodbutsuchtests are much more expensive than skin tests and should be used only in patients who cannot be skin-tested for some reason. Management Allergenavoidance Removal of a household pet or total enclosure of industrial processes releasing sensitizing agents can lead to cure of rhinitis and, indeed, asthma. The house-dust mite infests most areas of the house, but particularly the bedroom. Mite allergen exposure can be reduced by enclosing bedding in fabric specifically designed to preventthepassageofmiteallergen,whileallowingwatervapourthrough. Increased room ventilation and reduced soft furnishings, including carpets, curtains and soft toys, can all help to reduce the mite load. However, the value of house-dust mite control measuresinasthmahasbeenchallenged(seepp. Theyareparticularlyeffectiveagainstsneezinganditchingofthe eyes and palate, but are less effective against rhinorrhoea and have little influence on nasal blockage. First-generation antihistamines (chlorphenamine, hydroxyzine) cause sedation and loss of concentration in all patients (including those who are not aware of the problem) and should no longer be used. Second-generation drugs, such as loratadine (10mg once daily), desloratadine (5mg daily), cetirizine (10mg daily) and fexofenadine (120mg daily), are at leastaspotentanddonotcausesedation. Decongestants Drugs with sympathomimetic activity (-adrenergic agents) are widely used to treat nasal obstruction. Secondarynasalhyperaemiacanoccur somehourslaterasareboundeffectandrhinitismedicamentosacandevelopifpatientstake increasing quantities of decongestant to overcome this phenomenon. Anti-inflammatorydrugs Sodiumcromoglicateandnedocromilsodiumactbyblockinganintracellularchloridechannel and influence mast cell and eosinophil activation and nerve function. Corticosteroids the most effective treatment for rhinitis is a topical corticosteroid preparation. The combination of a topical corticosteroid with a non-sedating antihistamine taken regularly is particularly effective. Patients should be carefully instructed in how to use the nasal steroid devicetoachieveoptimaldrugdeposition. Inselectedcases,an-adrenergicagonistmayhelp to decongest the nose prior to taking the topical corticosteroid. Nasal polyps may respond to oral corticosteroids and their recurrence may be prevented by continuous use of topicalcorticosteroids. Immunotherapy this is used for patients with seasonal allergic rhinitis who have not responded to standard drugs. Endemic adenovirus infection causes the common sore throat, in which the oropharynxandsoftpalatearereddenedandthetonsilsareinflamedandswollen. Occasionally, localized epidemics occur due to adenovirus serotype 8, particularly in schools during summer, with episodes of fever, conjunctivitis, pharyngitis and lymphadenitis of the neck glands. Over several decades, the proportion of sore throats due to bacterial infections, such as haemolytic streptococcus, has fallen. Many different pathogens have been implicated in pharyngitisbutmostdonotrequirespecifictreatment. Persistentandseveretonsillitisshould be treated with phenoxymethylpenicillin 500mg four times a day or cefaclor 250mg three timesdaily. Acutelaryngotracheobronchitis Acute laryngitis is an occasional but striking complication of upper respiratory tract infections, particularly those caused by parainfluenza viruses and measles. Inflammatory oedema extends to the vocal cordsandtheepiglottis,causingnarrowingoftheairway;theremaybeassociatedtracheitis ortracheobronchitis. Progressiveairwaysobstructionmayoccur,withrecessionofthesofttissueof the neck and abdomen during inspiration and, in severe cases, central cyanosis. Thisisalife-threateningemergencyandrequiresurgent endotracheal intubation and intravenous antibiotics. Other manifestations of Hib infection are meningitis, septic arthritis and osteomyelitis. Influenza B is associated with localized outbreaks of mild disease, whereas influenza A causesworldwidepandemics(seep. Theillnessstartsabruptlywithafever, shivering and generalized aching in the limbs. This is associated with severe headache, sorenessofthethroatandadrycoughthatcanpersistforseveralweeks. Complications Secondarybacterialinfectioniscommonfollowinginfluenzavirusinfection,particularlywith Streptococcus pneumoniae and Haemophilus influenzae. Management is by bed rest and paracetamol, with antibiotics to prevent secondary infectioninthosewithchronicbronchitis,orcardiacorrenaldisease. Neuraminidaseinhibitorshelptoshortenthedurationofsymptomsinpatientswithinfluenza, if given within 48hours of the first symptom. Prophylaxis Protection by influenza vaccines is effective in only about 70% of people and lasts only for aboutayear. Nevertheless,routinevaccinationis recommended for all individuals over 65years of age and also for younger people with chronic heart disease, chronic lung disease (including asthma), chronic kidney disease or diabetes mellitus and for those who are immunosuppressed. Inhalationofforeignbodies Children inhale foreign bodies, such as peanuts, more commonly than do adults. In adults, inhalation may occur after excess alcohol or under general anaesthesia (loose teeth or dentures). There is a mild fever and a neutrophil leucocytosis; wheeze with occasional crackles can be heard on auscultation. The airflow limitation is usually both progressive and associated with an abnormalinflammatoryresponseofthelungstonoxiousparticlesorgases. Autopsy studies have shown substantial numbers of centriacinaremphysematousspacesinthelungsof50%ofBritishsmokersovertheageof60years, independentlyofwhethersignificantrespiratorydiseasewasdiagnosedbeforedeath. Theinflammation is followed by scarring and thickening of the walls, which narrows the small airways. The small airways are particularly affected early in the disease, initially without the developmentofanysignificantbreathlessness. Furtherprogressionoftheairwaysdiseaseleadstoprogressivesquamouscellmetaplasia and fibrosis of the bronchial walls. The physiological consequence of these changes is the development of airflow limitation. If the airway narrowing is combined with emphysema (causinglossoftheelasticrecoilofthelungwithcollapseofsmallairwaysduringexpiration), theresultingairflowlimitationisevenmoresevere. Emphysema is defined as abnormal, permanent enlargement of air spaces distal to the terminalbronchiole,accompaniedbydestructionoftheirwallsandwithoutobviousfibrosis. Suchpatientsappearlessbreathlessand,becauseofrenalhypoxia,theystart to retain fluid and increase erythrocyte production (leading eventually to polycythaemia). Pathogenesis Cigarettesmoking Bronchoalveolar lavage and biopsies of the airways of smokers show increased numbers of neutrophil granulocytes. These granulocytes can release elastases and proteases, which may help to produce emphysema. It has been suggested that an imbalance between protease and antiprotease activity causes the damage. Alpha1-antitrypsin is a major serum antiprotease, whichcanbeinactivatedbycigarettesmoke(seebelow). Mucous gland hypertrophy in the larger airways is thought to be a direct response to persistentirritationresultingfromtheinhalationofcigarettesmoke. Those who do develop breathlessness under the age of 40years have radiographicevidenceofbasalemphysemaandareusually,butnotalways,cigarettesmokers. Systemic effects include hypertension, osteoporosis, depression, weight loss and reduced musclemasswithgeneralweakness. Thefluidretention and peripheral oedema are due to failure of excretion of sodium and water by the hypoxic kidney rather than heart failure. Eveninadvanced disease, this may slow down the rate of deterioration and prolong the time before disability and death occur (see. Combinations of corticosteroids with long-acting 2 agonists may protect against lung function decline but do not improve overall mortality. Antibiotics Prompt antibiotic treatment shortens exacerbations and should always be given in acute episodes,asitmaypreventhospitaladmissionandfurtherlungdamage. Patientscanbegiven antibiotics to keep at home, starting them as soon as their sputum turns yellow or green. Theywereoncethoughttobeof no value, but eradication of infection and maintenance of the lower respiratory tract free of bacteriamayhelptopreventdeteriorationinlungfunction. Antimucolyticagents these reduce sputum viscosity and can reducethe number of acuteexacerbations. Oxygentherapy Two controlled trials (chiefly in males) have shown improved survival with the continuous administrationofoxygenat2L/minvianasalprongstoachieveanoxygensaturationof>90% forlargeproportionsofthedayandnight. Only 30% of those not receiving long-term oxygen therapy survived for more than 5years. A fall in pulmonary artery pressure was achieved if oxygen was given for 15 hoursdaily,butsubstantialimprovementinmortalitywasachievedonlybytheadministration of oxygen for 19hours daily. These nocturnal hypoxaemic episodes are associated with a further rise in pulmonary arterialpressureowingtovasoconstriction. Patients with arterial hypoxaemia should not be given sleeping tablets, as these will further depress respiratorydrive.
