GENERAL PRACTICE 2 - Sexual Health, Infect Dis, Derm, MSK Flashcards
What are some causes of erectile dysfunction?
Organic causes (80%)
* Cardiovascular CHD
* Diabetes Mellitus >35% of diabetic men have erectile dysfunction, May be the presenting feature of DM.
- Neurological, e.g. pelvic surgery, spinal injury, multiple sclerosis
Androgen deficiency – hypoth/pit/testes - Pituitary issue – adenoma. Prolactinoma stops the productions of gonadotrophins
- Side effects of prescription drugs
- Smoking (incidence i x2), alcohol, or drug abuse
Psychogenic causes
* Performance anxiety
* Depression or stress
* Relationship failure
* Fear of intimacy
What are some drugs that can cause erectile dysfunction?
thiazide diuretics and beta blockers
Finasteride - used to treat pattern hair loss and benign prostatic hyperplasia
Antidepressants (e.g. SSRIs)
antiandrogens
What examinations/causes/investigations should you be conisdering in Erectile dysfunction?
CVD and DM—check BP, peripheral pulses, and blood for fasting lipid
profile and glucose
* Psychological distress—consider depression/anxiety screening
* Testosterone insufficiency—genitals (small/absent), breasts i, d beard
(d frequency of shaving). If suspected, check serum testosterone,
What is the management for erectile dysfunction?
dentifying and treating any curable causes of ED
hormonal
androgen deficiency – treat with testosterone
Stop any drugs that are causing ED
initiating lifestyle change and risk factor modification - stop smoking, drink less
providing psychosexual/ relationship therapy, counselling to patients and their partners, CBT
first line medical treatment
Phosphodiesterase 5 inhibitors (e.g. sildenafil, tadalafil, vardenafil) are mainstays
vacuum erection devices:
What are some treatment options for premmature ejaculation?
se of daily selective serotonin reuptake inhibitor (SSRI)
Sertraline, Paroxetine and fluoxetine are recommended
application of topical anesthetic to reduce penile sensitivity, eg. lidocaine-prilocaine cream (5%) applied 20-30 minutes before sexual activity
behavioural techniques - . ‘Stop-start’ techniques, thicker condoms
taking breaks during sex
Couples therapy advice
What are some causes of Dyspareunia in females?
infection - especially, trichomonas, vaginal candidiasis
vaginal atrophy - postmenopausal shrinkage; infrequent intercourse
psychological - vaginismus, fear, ignorance, previous painful intercourse
poor sexual stimulation
pelvic inflammatory disease
endometriosis
What are some investigations for dyspareunia in females?
In majority of cases, investigations are not necessary.
vaginal and endocervical swabs if indicated
a urinalysis to reveal any UTI
a pelvic ultrasound – to check for hydrosalpinx and fibroids
laparoscopy if deep dyspareunia and cause is not apparent on examination
What is the treatment for dyspareunia in females?
Management typically focuses on treating underlying causes where appropriate
A penetration desensitisation programme is useful in dyspareunia and vaginismus
Fenton’s procedure - increase the dimensions of the introitus
intramuscular injection of botulinum toxin
Psychological therapy may be useful in some patients.
sensitive assessment and exploration of the woman’s fears and thoughts is important
issues connected with the birth of the child may be discussed with a counsellor
encourage the patient to talk to her partner and resolve any relationship difficulties they might have or refer them to a couples counsellor
if psychosexual problems persist refer her to a psychosexual therapist
What is reterograde ejacualtion? what can cause it?
Retrograde ejaculation Semen passes into the bladder rather than the urethra—complication of TURP or bladder neck incision.
May also occur as a result of spinal injury or DM. The patient can usually achieve an orgasm but there is no ejaculate or the volume of the ejaculate is decreased. Urine may be cloudy after having sex.
What is vaginismus, and what are some common causes of it?
Vaginismus Usually apparent at vaginal examination—severe spasm of the vaginal muscles and adduction of thighs.
Common causes:
* Fear of the unknown
* local pain
* Past history of rape, abuse, or severe emotional trauma
* Defence mechanism against growing up
What is the management of vaginismus?
progressive relaxation
used manage anxiety, and consists of alternately tensing and relaxing groups of muscles in a prescribed sequence e.g - beginning from the feet and moving upwards
desensitisation - vaginal trainers, and encouraging the woman to examine herself
physiotherapy
hypnotherapy
topical lidocaine applied within the vagina
antidepressants
What causes menopause?
- It is caused by a lack of ovarian follicular function, resulting in changes in the sex hormones associated with the menstrual cycle
- Oestrogen and progesterone levels are low
- LH and FSH levels are high in response to an absence of negative feedback from oestrogen
How does the menopause begin?
- The menopause begins with a decline in the development of ovarian follicles
- Without the growth and development of the follicles there is reduced production of oestrogen
- This results in increasing levels of LH and FSH as oestrogen has a negative feedback on these hormones in the pituitary gland
How can menopause be diagnosed?
- Symptoms without blood test
- Use FSH blood test in women under 40 or aged 40-45 with menopausal symptoms
What is the management of perimenopausal symptoms?
Hormone replacement therapy (HRT)
Tibolone, a synthetic steroid hormone that acts as continuous combined HRT (only after 12 months of amenorrhoea)
Clonidine, which act as agonists of alpha-adrenergic and imidazoline receptors
Testosterone can be used to treat reduced libido (usually as a gel or cream)
Vaginal oestrogen cream or tablets, to help with vaginal dryness and atrophy (can be used alongside systemic HRT)
Vaginal moisturisers, such as Sylk, Replens and YES
What can be used to help with the vasomotor symptoms of the menopause? The hot flushses and night sweats
Clonidine which is a alpha-2 agonist
What are the indications of HRT?
Replacing hormones in premature ovarian insufficiency, even without symptoms
Reducing vasomotor symptoms such as hot flushes and night sweats
Improving symptoms such as low mood, decreased libido, poor sleep and joint pain
Reducing risk of osteoporosis in women under 60 years
What are the risks of HRT
- Breast and endometrial cancer
- Angina
- Increased risk of VTE with oral pill
- Women are not at increased risk under 50
How does the COCP prevent pregnacy?
Preventing ovulation (this is the primary mechanism of action)
Progesterone thickens the cervical mucus
Progesterone inhibits proliferation of the endometrium, reducing the chance of successful implantation
the COCP contains both oestrogen and progesterone -what do these do in the body to act as contraception?
Oestrogen and progesterone have a negative feedback effect on the hypothalamus and anterior pituitary, suppressing the release of GnRH, LH and FSH.
No LH and FSH - ovulation cannot occur
With the COCP the lining of the endometrium is maintained in a stable state, will then have a withdrawal bleed when the pill is stopped
What are the two types of COCP and which are the main ones used?
Monophasic pills contain the same amount of hormone in each pill
Multiphasic pills contain varying amounts of hormone to match the normal cyclical hormonal changes more closely
The NICE Clinical Knowledge Summaries (2020) recommend using a pill with levonorgestrel or norethisterone first line (e.g. Microgynon or Leostrin). These choices have a lower risk of venous thromboembolism.
Microgeon or Loestrin
What are the side effects of COCP?
Unscheduled bleeding is common in the first three months and should then settle with time
Breast pain and tenderness
Mood changes and depression
Headaches
Hypertension
Venous thromboembolism (the risk is much lower for the pill than pregnancy)
Small increased risk of breast and cervical cancer, returning to normal ten years after stopping
Small increased risk of myocardial infarction and stroke
What are the contraindications of the COCP?
Uncontrolled hypertension
Migraine with aura
History of VTE
Aged 35 and smoking 15 cigarettes a day
Surgery
Vascular disease
IHD
Liver cirrhosis
SLE
How long after taking the pill are you protected
If started on day 1-5 of menstrual cycle then protection is immediate
If started after this then it takes 7 days to have protection
What COCPs can be used in the treatment of acne and hirsutism?
Dianette and other COCPs containing cyproterone acetate (i.e. co-cyprindiol) can be considered in the treatment of acne and hirsutism. Cyproterone acetate has anti-androgen effects, helping to improve acne and hirsutism.
Greater risk of VTE though
What is theoretial rules of protection when it comes to taking the pill?
What should you do if you miss one pill, but less than 72 hours since the last one was taken?
theoretically women will be protected if they perfectly take the pill in a cycle of 7 days on, 7 days off. This will prevent ovulation.
Missing one pill is when the pill is more than 24 hours late (48 hours since the last pill was taken).
Missing one pill (less than 72 hours since the last pill was taken):
Take the missed pill as soon as possible (even if this means taking two pills on the same day)
No extra protection is required provided other pills before and after are taken correctly
What should you do if you have missed more than one pill? (more than 72 hours since the last pill was taken)
Take the most recent missed pill as soon as possible (even if this means taking two pills on the same day)
Additional contraception (i.e. condoms) is needed until they have taken the pill regularly for 7 days straight
What should you do if you have missed more than one pill? (more than 72 hours since the last pill was taken), on days 1-7, 8-14, and 15-21?
If day 1 – 7 of the packet they need emergency contraception if they have had unprotected sex
If day 8 – 14 of the pack (and day 1 – 7 was fully compliant) then no emergency contraception is required
If day 15 – 21 of the pack (and day 1 – 14 was fully compliant) then no emergency contraception is needed. They should go back-to-back with their next pack of pills and skip the pill-free period.
Theoretically, additional contraception is not required if more than one pill is missed between day 8 – 21 (week 2 or 3) of the pill packet and they otherwise take the pills correctly, although it is recommended for extra precaution.
What are the two types of Progesterone only pill, and how long can you delay taking them for them still to be effective?
The traditional progestogen-only pill ( Norgeston or Noriday ) cannot be delayed by more than 3 hours. Taking the pill more than 3 hours late is considered a “missed pill”.
The desogestrel-only pill (Cerazette) can be taken up to 12 hours late and still be effective. Taking the pill more than 12 hours late is considered a “missed pill”.
What is the MOA of the tradiational progesterone only pill? ( Norgeston or Noriday )
Traditional progestogen-only pills work mainly by:
Thickening the cervical mucus
Altering the endometrium and making it less accepting of implantation
Reducing ciliary action in the fallopian tubes
What is the MOA of the Desogesterol-only pill? (Cerazette)
Desogestrel works mainly by:
Inhibiting ovulation
Thickening the cervical mucus
Altering the endometrium
Reducing ciliary action in the fallopian tubes
What is the only main thing that taking the POP is contraindicated in?
Active Breast Cancer
regarding the POP and COCP, if you want to be protected immediately, when in the menstraul cycle do you need to be taking it?
Both can be started within the first 5 days of the menstrual cycle and work immediately, as it is very unlikely a woman will ovulate this early in the cycle.
if you start taking the POP after day five of the menstrual cycle long would additional contraception be required for? Why?
It can be started at other times of the cycle provided pregnancy can be excluded. Additional contraception is required for 48 hours. It takes 48 hours for the cervical mucus to thicken enough to prevent sperm entering the uterus.
The POP can be started even if there is a risk of pregnancy, as it is not known to be harmful in pregnancy. However, the woman should do a pregnancy test 3 weeks after the last unprotected intercourse.
What are some side effects of the POP?
Changes to the bleeding schedule is one of the primary adverse effects of the progestogen-only pill. Unscheduled bleeding is common in the first three months and often settles after that.
Approximately:
20% have no bleeding (amenorrhoea)
40% have regular bleeding
40% have irregular, prolonged or troublesome bleeding
Other side effects include:
Breast tenderness
Headaches
Acne
What does the Progesterone only injection contain?
How long does it last for, as a method of contraception?
depot medroxyprogesterone acetate (a type of progestin). DMPA
Women need to have injections every 12 – 13 weeks. Delaying past 13 weeks creates a risk of pregnancy. The FSRH guidelines say it can be given as early as 10 weeks and as late as 14 weeks after the last injection where necessary, but this is unlicensed.
What is the MOA of the progesterone only injection?
The main action of the depot injection is to inhibit ovulation. It does this by inhibiting FSH secretion by the pituitary gland, preventing the development of follicles in the ovaries.
Additionally, the depot injection works by:
Thickening cervical mucus
Altering the endometrium and making it less accepting of implantation
What are the main side effects/risks for the Depot progesterone only injection
Changes to the bleeding schedule is one of the primary considerations with progestogen-only contraception.
Reduced bone mineral density (osteoporosis) = Oestrogen helps maintain bone mineral density in women, produced by the follicles in the ovaries.
Weight gain is also a key side
effect
Only form of contraception that causes weight gain and osteoporosis
What are the two kinds of contraceptive intrauterine device?
There are two types of intrauterine device (IUD):
Copper coil (Cu-IUD): contains copper and creates a hostile environment for pregnancy
Levonorgestrel intrauterine system (LNG-IUS): contains progestogen that is slowly released into the uterus
What things must be considered/down before a coil is inserted?
Screen for Chlamydia and Gonorrhoea before insertion of the coil in women at risk of STD (ie under 25 years old)
Perform Bimaniaul (pelvic) exam beforehand, to check postion and size of uterus
Record BP and heart rate before and after
If the threads of the coil cannot be seen on palpated, what 3 things need to be excluded?
When the coil threads cannot be seen or palpated, three things need to be excluded:
Expulsion
Pregnancy
Uterine perforation
Before the coil is removed, women need to abstain from sex or use condoms for 7 days, or there is a risk of pregnancy.
What are some drawbacks to having a coil fitted?
It can cause heavy or intermenstrual bleeding (this often settles)
Some women experience pelvic pain
It does not protect against sexually transmitted infections
Increased risk of ectopic pregnancies
Can fall out
Related to the IUS
There can be systemic absorption causing side effects of acne, headaches, or breast tenderness
What is the main type of IUS, and how long can it stay in for?
There are four types of IUS you may come across, all containing levonorgestrel:
Mirena: effective for 5 years for contraception, and also licensed for menorrhagia and HRT
The IUS to remember is the Mirena coil. It is commonly used for contraception, menorrhagia and endometrial protection for women on HRT. It is licensed for 5 years for contraception, but only 4 years for HRT.
How does the IUS (containing Levonorgesterel) work?
The LNG-IUS works by releasing levonorgestrel (progestogen) into the local area:
Thickening cervical mucus
Altering the endometrium and making it less accepting of implantation
Inhibiting ovulation in a small number of women
Give some benefits of coils
Copper:
Reliable contraception
It can be inserted at any time in the menstrual cycle and is effective immediately
It contains no hormones, so it is safe for women at risk of VTE or with a history of hormone-related cancers
It may reduce the risk of endometrial and cervical cancer
IUD:
Can make periods lighter
No effect on bone mineral density (unlike the depo injection)
No increase in thrombosis risk (unlike the COCP)
No restrictions for use in obese patients (unlike the COCP)
The Mirena has additional uses (i.e. HRT and menorrhagia)
outline some clinical symptoms regarding pain seen in fibromyalgia
Widespread muscle pain of >3 months
Pain
Pain worse with stress, cold weather activity
Morning stiffness <1 hour
Non-restorative sleep
Headache/diffuse abdominal pain
outline some clinical symptoms regarding neurocognition seen in fibromyalgia
Neurocognitive features
Poor sleep
Fatigue
Mood disorder
Poor concentration
Memory
Outline some of the pathophysiology that is thought to cause fibromyalgia.
Problems with pain signals
Low serotonin – inhibits pain signals
Raised substance P and nerve growth factor – increased pain signals
How would you diagnose fibromyalgia?
Diagnosis of fibromyalgiais based on clinical features:
- Chronic pain that has been present for at least 3 months
- Widespread pain - involved left and right sides, above and below waist, and the axial skeleton.
- Palpate tender point sites - severe pain in 3 to 6 different areas of your body, or you have milder pain in 7 or more different areas
- No other reason for symptoms has been found
What investigations would you do in suspected fibromyalgia to rule out other conditions can could cause the symptoms seen?
TFTs – rule out hypothyroidism
ANAs and dsDNA – to exclude SLE
ESR and CRP – to exclude Polymyalgia rheumatica (PMR)
Calcium and electrolytes – to exclude high calcium
Vitamin D – to rule out low vitamin D
Examine patient and CRP – to rule out inflammatory arthritis
What are some non pharmalogical measures for fibromyalgia?
MDT approach advise there is not one specific treatment that will defo work
Regular exercise for CV fitness eg fast walking, biking, swimming, or water aerobics can help by reducing pain and fatigue.
- Relaxation techniques and good sleep hygiene can also help.
- Physiotherapy and rehabilitation
- CBT
What are some pharmacological measures to help manage fibromyalgia
- Amitriptyline - tricyclic antidepressant
- Serotonin-norepinephrinereuptake inhibitors (SNRIs) e.g. duloxetine
Anticonvulsants like pregabalin and gabapentinwhich slow nerve impulses
Steroids or NSAIDS are not recommended because
there is no inflammation (if it does respond, reconsider your diagnosis!)
What is otitis externa?
Otitis externa is a condition that causes inflammation (redness and swelling) of the external ear canal, which is the tube between the outer ear and eardrum.
What is the presentation of Otitis externa
Ear pain
Discharge
Itchiness
Conductive hearing loss (if the ear becomes blocked)
Examination can show:
Erythema and swelling in the ear canal
Tenderness of the ear canal
Pus or discharge in the ear canal
What is the treatment of otitis externa?
advise analgesia, e.g. paracetamol 9 ibuprofen
* prescribe ear drops—options are: aluminium acetate drops (as effective as antibiotics); and antibiotic and/or steroid drops
Avoid going in water/inserting things into your ear
Skin of the pinna adjacent to the ear canal is often affected by eczema.
Treat with topical corticosteroid cream/ointment—avoid prolonged use
What is malignant/necrotising otitis externa and what are the risk factors?
The infection spreads to the bones surrounding the ear canal and skull. It progresses to osteomyelitis of the temporal bone of the skull.
Diabetes
Immunosuppressant medications (e.g., chemotherapy)
HIV
What is otitis media?
- Infection of the middle ear which is the space that sits between the tympanic membrane and the inner ear
- This is where the nerves are found
What causes otitis media?
- Bacteria enter from the back of the thorat through the eustachian tube - Strep pneumoniae is most common
- A Viral URTI often precedes otitis media
What is the presentation of otitis media?
- Ear pain
- Reduced hearing
- Feeling unwell
- Signs of URTI
Examination otitis media?
- Otoscope tympanic membrane will look bulging red and perforation will show discharge and hole in tympanic membrane
Management otitis media?
Most otitis media cases will resolve without antibiotics within around three days, sometimes up to a week. Antibiotics make little difference to symptoms or complications.
Amoxicillin for 5-7 days first-line
Clarithromycin (in pencillin allergy)
Erythromycin (in pregnant women allergic to penicillin)
What is otitis media with effusion? When should you think about it?
Its inflammation and accumulation of fluid in the middle ear, without any symptoms of acute inflammation
Earache/hearing loss may not be present
Behavioural problems should alert the GP to assess a child for OM with effusion
What is fungal infections of the skin called, and what are the specific names
Ringworm is a fungal infection of the skin and also known as tinea Fungal infections have specific names depending on the area they affect:
Tinea capitis refers to ringworm affecting the scalp (caput meaning head)
Tinea pedis refers to ringworm affecting the feet, also known as athletes foot (pedis meaning foot)
Tinea corporis refers to ringworm on the body (corporis meaning body)
Onychomycosis refers to a fungal nail infection
How does Ringworm present with, specifically
Tinea Capitis,
Tinea Pedis, and
Onychomycosis?
Ringworm presents as an itchy rash that is erythematous, scaly and well demarcated.
Tinea capitis can present with well demarcated hair loss. There will also be itching, dryness and erythema of the scalp. This is more common in children than adults.
Tinea pedis (athletes foot) presents with white or red, flaky, cracked, itchy patches between the toes. The skin may split and bleed.
Onychomycosis (fungal nail infections) presents with thickened, discoloured and deformed nails.
TOM TIP: Check the toenails in someone presenting with ringworm, you may find they have a fungal nail infection that has spread to the skin.
What is the management for ringworm?
Treatment of ringworm is with anti-fungal medications:
Anti-fungal creams such as clotrimazole and miconazole
Anti-fungal shampoo such as ketoconazole for tinea capitis
Oral anti-fungal medications such as fluconazole, griseofulvin and itraconazole
What causes scabies? How long can it take for symptoms to appear with it after the initial infestation?
Scabies are tiny mites called Sarcoptes scabiei that burrow under the skin causing infection and intense itching. They lay eggs in the skin, leading to further infection and symptoms.
It can take up to 8 weeks for any symptoms or rash to appear after the initial infestation.
What is the presentation of scabies
Scabies presents with incredibly itchy small red spots, (papular rash) possibly with track marks where the mites have burrowed.
The classic location of the rash is between the finger webs, but it can spread to the whole body.
Itching tends to be worse at night.
What is the treatment of scabies
Treatment is with permethrin cream. This needs to be applied to the whole body, completely covering skin. It is best to do this when the skin is cool (i.e. not after a bath or shower)
The cream should be left on for 8 – 12 hours and then washed off. This should be repeated a week later to kill all the eggs that survived the first treatment and have now hatched.
When one person is diagnosed, all household and close contacts should also be treated in exactly the same way, even if asymptomatic. This is because they may be infected and not yet have symptoms.
What are warts, and what is the main cause of them?
Warts are non-cancerous viral growths usually occurring on the hands and feet but can also affect other locations, such as the genitals or face.
Warts are caused by the human papillomavirus (HPV). There are about 130 known types of human papillomaviruses.
HPV infects the squamous epithelium, usually of the skin or genitals
What is the treatment for warts?
Salicylic acid (wart paints), or cryotherapy
What is mumps? what percentage of protection does the mump vaccine offer?
Mumps is a viral infection spread by respiratory droplets.
Taking a vaccination history is essential when considering a diagnosis of mumps. The MMR vaccine offers around 80% protection against mumps.
How long do symptoms take for show in mumps, and what is the clinical presentation
Patients experience an initial period of flu-like symptoms known as the prodrome. These occur a few days before the parotid swelling:
Fever
Muscle aches
Lethargy
Reduced appetite
Headache
Dry mouth
Parotid gland swelling, either unilateral or bilateral, with associated pain is the key feature that should make you consider mumps.
What is the management of mumps?
The diagnosis can be confirmed using PCR testing on a saliva swab. The blood or saliva can also be tested for antibodies to the mumps virus.
Mumps is a notifiable disease, meaning you need to notify public health of any suspected and confirmed cases.
Management is supportive, with rest, fluids and analgesia. Mumps is a self limiting condition. Management of complications is also mostly supportive.
What are some of complications of mumps?
It can also present with symptoms of the complications, such as:
Abdominal pain (pancreatitis)
Testicular pain and swelling (orchitis)
Confusion, neck stiffness and headache (meningitis or encephalitis)
What bacteria causes Lyme disease?
B burgdorferi
What are the symptoms of Lyme disease?
- Tick bite with rash called erythema migrans - (resembles a bulls eye)
- Fever
- Headache
- Myalgias
- Stiff neck
- Facial palsy
What is the treatment for Lyme disease?
Doxycycline, unless there is just a rash that can’t be distinguished from cellulitis then use amoxicillin
What causes infectious mononucleosis - and how can it be spread
nfection with the Epstein Barr virus (EBV). It is commonly known as the “kissing disease”, “glandular fever” or “mono”
This virus is found in the saliva of infected individuals. Infection may be spread by kissing or by sharing cups, toothbrushes and other equipment that transmits saliva.
What are some symptoms of infectious mononucleosis
Features
Fever
Sore throat
Fatigue
Lymphadenopathy (swollen lymph nodes)
Tonsillar enlargement
Splenomegaly and in rare cases splenic rupture
Virus targets circulating B lymphocytes (lifelong latent infection) and squamous epithelial cells of oropharynx
Antibody tests for infectious mononucleosis - what is the heterophile antibodies? Outline its sensitivity and specificity
In infectious mononucleosis, the body produces something called heterophile antibodies, which are antibodies that are more multipurpose and not specific to the EBV antigens (takes 6 weeks for them to be produced)
Monospot test: this introduces the patient’s blood to red blood cells from horses. Heterophile antibodies (if present) will react to the horse red blood cells and give a positive result.
Paul-Bunnell test: this is similar to the monospot test but uses red blood cells from sheep.
These tests are almost 100% specific for infectious mononucleosis, however not everyone who has IM produces heterophile antibodies, and it can take up to six weeks for the antibodies to be produced. Therefore they are only 70 – 80% sensitive.
What is the management for infectious mononucleosis?
- Is usually self-limiting and lasts 2-3 weeks but can cause fatigue for several months
What can cause a rash in infectious mononucleosis?
Mononucleosis causes an intensely itchy maculopapular rash in response to amoxicillin or cefalosporins.
Look out for the exam question that describes an adolescent with a sore throat, who develops an itchy rash after taking amoxicillin
What is the advice given to patients with infectious mononucleosis?
- Avoid alcohol as EBV impacts the livers ability to process it
- Avoid contact sports due to risk of splenic rupture
What are the complications of infectious mononucleosis?
Splenic rupture
Glomerulonephritis
Haemolytic anaemia
Thrombocytopenia
Chronic fatigue
EBV infection is associated with certain cancers, notable Burkitt’s lymphoma.
What groups of people are offered a yearly flu vaccine, free on the NHS?
Aged 65 and over
Young children
Pregnant women
Chronic health conditions, such as asthma, COPD, heart failure and diabetes
Healthcare workers and carers
What are some presenting features of being infected with the influenza virus?
Delay between exposure/Sx typically ~2d
Fever
Lethargy and fatigue
Anorexia (loss of appetite)
Muscle and joint aches
Headache
Dry cough
Sore throat
Coryzal symptoms
Give some differences between a presentation of flu, and a presentation of the common cold
Flu tends to have an abrupt onset, whereas a common cold has a more gradual onset. Fever is a typical feature of the flu but is rare with a common cold. Finally, people with the flu are “wiped out” with muscle aches and lethargy, whereas people with a cold can usually continue many activities.
What are some investigations for those with the influenza virus?
Point-of-care tests using swabs are available, giving a rapid result. They detect viral antigens
Viral nasal or throat swabs can be sent to the local virology lab for polymerase chain reaction (PCR) analysis
What is some treatment for:
Those at risk of complications of influnza virus
Those who need post exposure prophylaxis - aka chronic diseasee/immunosuppression
For complications
* Oral oseltamivir (BD for 5d)
Inhaled zanamivir (BD for 5d)
PEP
* Oral oseltamivir 75mg OD for 1od
Inhaled zanamivir 10mg OD for 10d
What are some complications of influenza virus ?
Otitis media, sinusitis, bronchitis
Viral pneumonia
2y bacterial pneumonia
Worsening chronic health conditions - COPD, HF
Febrile convulsions (young children)
Encephalitis
What would someone with primary syphilis present with?
A painless genital ulcer (chancre). This tends to resolve over 3 – 8 weeks.
Local lymphadenopathy
What would someone with secondary syphilis present with?
ypically starts after the chancre has healed, with symptoms of:
Maculopapular rash
Condylomata lata (grey wart-like lesions around the genitals and anus)
Low-grade fever
Lymphadenopathy
Alopecia (localised hair loss)
Oral lesions
How can you test for syphilis?
Antibody testing for antibodies to the T. pallidum bacteria can be used as a screening test
or
Samples from sites of infection can be tested to confirm the presence of T. pallidum with:
Dark field microscopy
Polymerase chain reaction (PCR)
What is the management for syphilis
. As with all sexually transmitted infections, patients need:
Full screening for other STIs
Advice about avoiding sexual activity until treated
Contact tracing
Prevention of future infections
A single deep intramuscular dose of benzathine benzylpenicillin (penicillin) is the standard treatment for syphilis.
What are the most common bacterial causes of tonsillitis?
bacterial tonsillitis = group A streptococcus pyogenes
2nd MC cause bacterial = streptococcus pneumoniae
Other bacterial causes:
H.influenzae
M.catarrhalis
S.aureus
What are the most commonly affected tonsilis in tonsilitis?
Waldeyer’s tonsillar ring
- In pharynx at back of throat = ring of lymphoid tissue
- 6 areas of lymphoid tissue in Waldeyer’s ring (adenoids, tubal tonsils, palatine tonsils + lingual tonsil)
- Palatine tonsils typically infected & enlarged in tonsillitis = tonsils at either side at back of throat
What are some signs and symptoms of tonsillitis?
O/E - throat red, inflamed, enlarged tonsils ± exudates (small white patches of pus on tonsils)
Tonsillar erythema + enlargement
Also may be anterior cervical lymphadenopathy (swollen, tender lymph nodes in anterior triangle of neck) ==> Tonsillar lymph nodes just behind angle of mandible
Sore throat (sudden onset)
Fever (above 38º)
Pain on swallowing
Headache
Abdo pain
What is the centor criteria?
- Used to estimate the probability that the tonsillitis is due to a bacterial infection
Fever over 38
Tonsillar exudates
Absence of cough
Tender cervical lymph nodes
A score of 3 or more indicates a 40-60% likelihood it is bacterial
What is the fever PAIN score?
A score of 2 – 3 gives a 34 – 40% probability, and 4 – 5 gives a 62 – 65% probability of bacterial tonsillitis:
Fever during previous 24 hours
P – Purulence (pus on tonsils)
A – Attended within 3 days of the onset of symptoms
I – Inflamed tonsils (severely inflamed)
N – No cough or coryza
What is rhinosinusitis?
Sinusitis refers to inflammation of the paranasal sinuses in the face. This is usually accompanied by inflammation of the nasal cavity and can be referred to as rhinosinusitis.
What is the basic anatomy of the paranasal sinuses, and what causes sinusitis?
The paranasal sinuses are hollow spaces within the bones of the face, arranged symmetrically around the nasal cavity. They produce mucous and drain into the nasal cavities via holes called ostia. Blockage of the ostia prevents drainage of the sinuses, resulting in sinusitis.
Derm - Define what is meant by macular, or what a macular rash would look like
Flat, nonpalpable lesion with color change (hyper- or hypopigmented, erythematous) less than
5-10mm
Derm - Define what is meant by papule, or what a papular rash would look like
Raised lesion less than 5-10 mm (wart, actinic keratosis)
Derm - Define what is meant by a vesicle, or what a vesicular rash would look like
Name some conditions where you may see some
Well circumscribed fluid-filled lesion up to 5-10mm - seen in herpes, Varicella
What is the definition of a macular papular rash?
Give some diseases where you may see it
A maculopapular rash is a mix of macules (flat discolored areas of skin) and papules (small raised bumps) that usually cover a large area of skin.
scarlet fever, measles, secondary syphilis, rubella, HIV,
What is the presentation of measles?
Known as first disesase (of the 6 original viral exanthemas)
fever, conjunctivitis, coryza, diarrhea, Koplik spots (white spots on the red buccal mucosa, like small grains of sand)
Then generalized, maculopapular rash, classically face/neck->trunk->limbs
What is the treatment for measles?
Supportive. Isolate children in hospital. In immunocompromised patients, antiviral drug ribavirin can be used.
Vitamin A, which may modulate the immune
response should be given in low-income countries.
Prevention by immunization is the most successful
strategy for reducing the morbidity and mortality of
measles.
What are some signs and symptoms of scarlet fever
Erythematous ‘pinhead’ Sandpaper rash, spares the face, desquamates around the fingers and toes + ‘Strawberry tongue’
Fever, Malaise, headache, nausea.
Scarlet fever usually follows from a group A streptococcal infection
What is the treatment for scarlett fever?
Swab throat
Prescribe a 10-day course of phenoxymethylpenicillin (penicillin V) first-line.
Azithromycin if allergic
What are the signs of a Rubella infection? How is it treated?
The maculopapular rash is often the first sign of infection, appearing initially on the face and then spreading centrifugally to cover the whole body. It fades in 3 days to 5 days.
Lymphadenopathy, particularly the suboccipital and
postauricular nodes, is prominent.
May have low grade fever
There is no effective antiviral treatment, so immunisation is key
What is slapped cheek syndrome, and what causes it?
Known as fifth disesase (of the 6 original viral exanthemas)
(fourth disease, or Dukes disease, isn’t really a thing anymore btw)
one of several possible manifestations of infection by parvovirus B19.
It typically presents as a rash and is more common in children
Also known as Erythma Infectiosum, or fifth disease
What are some symptoms of slapped cheek syndrdome, and how does it affect the body?
HPV-B19 infects the erythroblastoid red cell precursors
in the bone marrow.
asymptomatic infection – common; about 5% to
10% of preschool children and 65% of adults have
antibodies
* erythema infectiosum – the most common illness,
with a viraemic phase of fever, malaise, headache,
and myalgia followed by a characteristic rash on
the face (slapped-cheek) a week later, progressing
to a maculopapular, ‘lace’-like rash on the trunk
and limbs;
arthralgia or arthritis can be common in adults
What is the pattern of illness seen in roseola?
It presents 1 – 2 weeks after infection with a high fever (up to 40ºC) that comes on suddenly, lasts for 3 – 5 days and then disappears suddenly.
There may be coryzal symptoms, sore throat and swollen lymph nodes during the illness.
When the fever settles, the rash appears for 1 – 2 days. The rash consists of a mild erythematous macular rash across the arms, legs, trunk and face and is not itchy.
The main complication to be aware of is febrile convulsions, due to high temperature
What are the 4 main types of psoarisis?
Plaque psoriasis
Guttate psoriasis
Pustular psoriasis
Erythrodermic psoriasis
Outline what is seen in Plaque psoriasis
Thickened erythematous plaques (1-10cm diameter)
Silver scales
Commonly seen extensor surfaces and scalp
MC form in adults
Skin changes caused by rapid generation of new skin cells
Results in abnormal build up/thickening of skin
Outline what is seen in guttate psoriasis - what is it often triggered by?
2nd MC form, commonly occurring in children
Many small raised papules (mildly erythematous, scaly)
Across trunk and limbs
Over time papules -> plaques
Often triggered by streptococcal throat infection/stress/meds
Often spontaneously resolves 3-4mths
Outline what is seen in Pustular and Erythrodermic psoriasis
Both rare, and medical emergency
Pustular - Pustules form under skin, pts can be systemically unwell
erythrodermic -Extensive erythematous inflamed areas, covering a large SA of skin - skin comes away in large patches
What are some features of a presentation of psoriasis? Where is it often seen, and what can it be associated with?
Typically erythematous, circumscribed scaly papules and plaques on elbows, knees, extensor surfaces of limbs, scalp, and, less commonly, nails, ears, and umbilical region.
Pruritus
Also associated with:
Nail psoriasis (pitting, thickening, discolouration, ridging & onycholysis)
Psoriatic arthritis
Psychosocial implications - depression, anxiety
Plaques, erythematous, painful regions
Bottom right - Gauatte psoriasis, and rest - plaque psoriasis
What are some specific signs you may see in a pt with psoriasis?
Auspitz sign refers to small points of bleeding when plaques are scraped off
Koebner phenomenon refers to the development of psoriatic lesions to areas of skin affected by trauma (psoriasis on scars)
Residual pigmentation of the skin after the lesions resolve
What is Folliculitis?
Folliculitis is the infection and inflammation of one or more hair follicles.
Manifests clinically as erythematous papules or pustules around hair follicles
What is Urticaria?
What is the pathophysiology behind it?
Urticaria are also known as hives. They are small itchy lumps that appear on the skin. They may be associated with a patchy erythematous rash.
Urticaria are caused the release of histamine and other pro-inflammatory chemicals by mast cells in the skin.
This may be part of an allergic reaction in acute urticaria or an autoimmune reaction in chronic idiopathic urticaria.
What is the pathophysiology of OA?
It appears inflammatory cytokines interrupt normal repair of cartilage damage.
(IL-1) (TNF-alpha) stimulate metalloproteinase production which degrade the collagen and proteoglycans, and inhibits collagen production
As cartilage is lost, the joint space narrows. Bone on bone interaction may occur, leads to stress and over time subchondral sclerosis (via a process called eburnation) seen on x-ray.
Essentially, cartilage is lost and chondroblasts are unable to replace and repair the lost cartilage, this leads to abnormal bone repair.
What are the symptoms of OA?
Joint pain - exacerbated by movement and relieved by rest
Worse as the day goes on
Joint Stiffness
Swelling
OFTEN ASSYMETIRCAL
Joint Locking - inability to straighten joints
What are the clinical signs of OA?
Hands:
Bouchard’s Nodes
Heberden’s Nodes
Thenar Muscle wasting
First CMC Joint affected most
Weak grip
Knees:
Crepitus
Hips:
Antalgic gait
Restricted internal rotation
All affected Joints:
Joint tenderness
What is Heberden’s and Bouchard’s Nodes?
Bouchard’s - Bony swelling at PIP - (tom has this on his deformed finger)
Heberden’s Bony swelling at the DIP
Remember B before H and proximal before distal
What are the primary investigations to diagnose OA?
Joint X rays show OA hallmarks: LOSS:
Loss of Joint space
Osteophytes
Subarticular Sclerosis
Subchondral Cysts
Outline the pathophysiology behind RA - what do the autoantibodies produced by plasma cell as and T cells go on to do? 2
enter the circulation and reach the joints.
Here, T cells secrete cytokines (e.g. Interferon-gamma and IL-17) = recruits macrophages. Macrophages also produce cytokines (TNF, IL-1 and IL-6)
These makes the Synovial cells proliferate, making a Pannus.
What are two autoantibodies that are found in rheumatoid arthritis?
What can chronic inflammation lead to?
- Rheumatoid factor - IgM antibody that targets altered IgG
- Anti-CCP anti-cyclic citrullinated peptide - targets citrullinated proteins. = forms an immune complexes, that activate complement system,
Chronic inflammation can also cause angiogenesis, allowing more inflammatory cells to arrive.
What other parts of the body can RA affect?
Inflammatory cytokines can also escape the joint space and affect multiple organ systems
Brain
Lungs
Heart
Eyes
Liver
Blood vessels
What are some issues that RA can cause when it spreads to other areas of the body? (Brain, lungs, eyes, liver, blood vessels)
fever in brain, Peripheral neuropathy
Lungs - Plural Effusions/ pulmonary fibrosis
Heart - Increased IHD risk, Pericarditis, MI
Eyes -Episcleritis
Liver - Increase in Hepcidin, which leads to less iron absorption in the blood - Anaemia
Blood - Atherosclerotic Plaque deposition, Vasculitis
Renal - Glomerulonephritis
Oral - Sjogrens Syndrome
Rheumatoid skin nodules
Signs of Rheumatoid arthritis - what is
- Boutonniere deformity:
- Swan-neck deformity:
- Z-thumb deformity: ??
- Boutonniere deformity: PIP flexion and DIP hyperextension
- Swan-neck deformity: PIP hyperextension and DIP flexion
B before S, so in Boutonniere - F before H, and Swan Neck - H before F
- Z-thumb deformity: hyperextension of the thumb IP joint with flexion of the MCP joint.
What investigations would you do for Rheumatoid arthritis?
Serology -
Rheumatoid factor (RF)
anti-cyclic citrullinated peptide (anti-CCP) antibody
ESP and CRP will be elevated
May show anaemia of chronic disease - Low Hb Count
Joint x-rays -
Do baseline Kidney and liver functions, as will need to monitor these if on DMARDs
What would you see on an x ray for rheumatoid arthritis?
can see
X-ray – LESS
Loss of joint space
Erosions (peri-articular)
Soft tissue swelling
Soft bones (osteopenia)
What is the first-lie monotherapy for rheumatoid arthritis?
Disease-Modifying Anti-Rheumatic Drugs (DMARDs)
Any one of methotrexate, leflunomide or sulfasalazine.
Hydroxychloroquine can be considered in mild disease, mildest anti rheumatic drug
METHOTREXATE - TAKE ONCE A WEEK, SUPPLEMENTING FOLIC ACID AS WELL
after Disease-Modifying Anti-Rheumatic Drugs (DMARDs), what else can you give in rheumatoid arthritis?
Biologics:
Abatacept - Suppress T Cells
Rituximab - Suppress B Cells
T cell drug ends in T, B cell drug ends in B
Infliximab, or etanercept - Suppress TNF a
Anakinra - Suppress IL-1
Oultline some differences between RA and Osteoarthritis
osteoarthritis
Morning stiffness <30mins
Affects older people more
Cartilage loss
Degenerative disease
Asymmetrical
Can affects DIP joint
Rheumatoid Arthritis
Morning stiffness >60 mins
Joints hot and red
affects younger people
Symmetrical
Inflamed Synovium
Autoimmune disease
rarely effects DIP joint
What factors can increase uric acid production?
Malignancy - increased cell turnover
Cytotoxic drugs
Purine rich diet - seafood and alcohol, red meat
Obesity
Psoriasis
Increased production of purines - seen in high fructose corn syrup drink like tango, fanta
What are the decreased secretion of uric acid causes of gout?
CKD
Diuretics e.g., thiazide and loop
Dehydration,
Alcohol intake
Lead toxicity
High fructose intake
Describe the pathophysiology of gout?
Uric acid is formed as a breakdown product if purines
Uric acid has a limited solubility in the blood
If too much urate accumulates, it’ll turn into urate ion and bind to sodium, forming monosodium urate crystals
This forms urate crystals which deposit in areas with slow blood flow the joints and kidney tubules
What the signs of Gout and where is affected?
What are deposits of uric acid called?
Gout tophi are deposits of uric acid
Ears
Most common site in gout is 1st MTP joint
Base of big toe Podagra - gout of the foot
Wrists
Base of thumb
How would you diagnose gout?
Can be made on just clinical presentation but excluding septic arthritis is key
Joint aspiration and analysis of Synovial fluid will show:
no bacterial growth,
Needle shaped crystals, displaying Negative bifringement under polarised light
undergoing polarised microscopy
Monosodium urate crystals
Measure serum urate levels 4-6 weeks after attack as they can be low at time of attack
What is the first line and second line + 3rd line treatment for gout?
1st line - NSAIDs – naproxen, ibuprofen
2nd line - Colchicine (if NSAIDs contraindicated i.e. peptic ulcer, diabetes, renal disease) - Inhibits WBC migration
3rd line - Steroids
remember that colchicine was also seen in treatment for pericarditis?
What is given to prevent gout?
Lifestyle management and a Xanthine oxidase inhibitor
First-line Allopurinol
Describe the pathophysiology of pseudogout?
What is produced as a result?
Deposition of calcium pyrophosphate triggers synovitis with the knee, shoulder and wrist most commonly being affected
Produces the radiological appearance of chondrocalcinosis (linear calcification parallel to the articular surfaces)
Can be acute or chronic
What investigations should you do for suspected pseudo gout? What is a key one to do in order to rule out a another condition that would be a medical emergency?
Joint aspiration:weakly-positively birefringent rhomboid-shaped crystals under polarised microscopy confirm the diagnosis.
If any bacterial growth, then patient is likely to have septic arthritis - MEDICAL EMERGENCY
Joint X-ray:chondrocalcinosis (calcification of articular cartilage) is seen in 40% of casesand is highly suggestive of pseudogout but is not diagnostic; theabsenceof chondrocalcinosis doesnotexclude pseudogout
FBC – raised WBCs
Pseudogout - positive birefringent crystals
What screening tool can you use in osteoporosis?
FRAX = fracture risk assessment tool
Predicts the risk of a fragility fracture over the next 10 years. Usually the first step of assessment and is done on patients at risk of osteoporosis
BMI, co-morbidities, smoking, alcohol and family history +/- bone mineral density
- It gives results as a percentage 10 year probability of a:
- Major osteoporotic fracture
- Hip fracture
What T scoring on a DEXA scan would be indicative of
Better than reference
No evidence of oesteoporosis
Osteopenia (offer lifestyle advice)
Osteoporosis
T-score
>0 BMD = is better than the reference.
0 to -1 = BMD is in the top 84%: no evidence of osteoporosis.
-1 to -2.5 = Osteopenia. Risk of later osteoporotic fracture. Offer lifestyle advice.
-2.5 or worse = Osteoporosis. Offer lifestyle advice and treatment Repeat DEXA in 2yrs.
What are some other treatment options for osteoporosis?
Hormone replacement therapy should be considered in women that go through menopause early.
Raloxifene - Selective oestrogen receptor
Teriparatide - recombinant PTH, increases bone formation
What are the primary investigations of GCA?
1st line:
INCREASED ESR - ELEVATED IN 83% OF CASES
ANCA Negative
Temporal Artery biopsy - diagnostic
Fundoscopy
Picture - diagnostic criteria
What is ankylosing spondylitis?
A chronic progressive inflammatory arthropathy. It mainly affects the spine and cause progressive stiffness and pain.
Ankylosis= abnormal stiffening and immobility of a joint due to the fusion of a bone
Outline the pathophysiological process behind Ankylosing Spondylitis.
Inflammation destroys the intervertebral joints, facet joints and sacroiliac joints
Fibroblasts replace the destroyed joints with fibrin 🡪 formation of tough fibrin band around joints which limits range of motion
Ossification occurs (fibrous tissue turns to bone) and makes spine immobile
Syndesmophytes – new bone formation and vertical growth from anterior vertebral corners
What investigations would you do for someone with ankylosing spondylitis?
- CRP and ESR - elevated
- Genetic testing - HLA-B27?
- Early stages - MRI of spine if x-ray is normal - can show early changes which show up as bone marrow oedema (red arrows) as well as erosions, sclerosis and ankylosis
Give the order of management for Ankylosing spondyltis.
Physio and hydrotherapy
Long term high dose NSAIDs e.g. ibuprofen or naproxen
DMARDs e.g. methotrexate – treat peripheral arthritis but not the disease
Biologics– Anti-TNF e.g. etanercept or monoclonal antibodies against TNF e.g. infliximab,
Monoclonal antibodies targeting IL-7 - e.g. secukinumab
What is reactive arthritis?
An arthritis that is triggered following an infection (probs by molecular mimicry)
Also known as Reiter syndrome
Its a type of Seronegative spondyloarthropathy - RF is absent
Outline the pathophysiology that is thought to be behind reactive arthritis
Thought that the lipopolysaccharide (Endotoxin) on the gram negative bacteria produces a particularly strong response from immune system.
This response also results in antibodies or inflammation that also affect the joints.
In reactive arthritis, there are no actual joint infections (as seen in septic arthritis). The infection is at another site!
What is the key presentation of reactive arthritis?
Acute, asymmetrical monoarthritis typically in lower leg (knee).
Can also present with triad of: Urethritis, arthritis and conjunctivitis
Can’t see, pee or climb a tree THIS TRIAD IS KNOWN AS REITER’S SYNDDROME
What are the investigations for reactive arthritis?
- ESR and CRP - elevated
- Infectious serology ask about history of infection
- Genetic testing for HLA-B27
- If diarrhoea - culture stool
Aspirate joints to rule out septic arthritis/Gout - should be sterile in RA
Sexual health review
What is the management of Reactive arthritis?
Management
Treat cause of infection – antibiotics
NSAIDs ± steroid joint injections
Consider use of methotrexate and sulfasalazine as steroid sparing agents if >6 months
- Recurrent/ persistent reactive arthritis
- DMARDs e.g. methotrexate or sulfasalazine
- Anti-TNF
What is septic arthritis? What are the two ways in which it can occur?
Septic arthritis is defined as the infection of 1 or more joints caused by pathogenic inoculation of microbes.
It occurs either by direct inoculation or via haematogenous spread.
It is a medical emergency!- CAN AFFECT ANY JOINT, MOST COMMONLY KNEE
What are the signs and symptoms of septic arthritis?
Normally only one joint is affected. Most commonly the knee.
Hot tender and swollen joint
Limited range of movement
Difficulty weight bearing
Fever
What investigations would you do for septic arthirits? What is gold standard?
- FBC: leukocytosis
- CRP and ESR: elevated due to inflammation and used for monitoring response to treatment
- Blood cultures: should be performed onallpatients before commencing antibiotics
Joint aspiration (arthrocentesis): definitive investigation ideally prior to commencing antibiotics; synovial fluid should be sent to the lab for microscopy and culture
What is the management for Septic arthritis?
- IV antibiotics
- Empirical therapy: flucloxacillin is first-line
- Penicillin allergy: clindamycin
- Suspected or confirmed MRSA: vancomycin
- Gonococcal arthritis or gram-negative infection: cefotaxime or ceftriaxone
-
Joint drainage
- Aspiration
- Arthroscopic drainage
- Open drainage
What is osteomyelitis?
Inflammation of the bone marrow (infection localised to bone) caused by an infecting organism, most commonly Staphylococcus aureus.
What bacteria can cause osteomyelitis?
- Staphylococcus aureus:A gram-positive cocci. Includes MRSA - MOST COMMON
- Pseudomonas aeruginosa:A gram-negative rod. More commonly seen in IV drug users.
- Salmonellaspp.:Gram-negative rods. Most commonly seen in patients with sickle cell anaemia.
What are some risk factors for getting osteomyelitis?
Diabetes mellitus - vascular compromise due to high blood sugar
Trauma – bone exposed to outside environment (open fractures)
Surgery
Peripheral vascular disease
Malnutrition
Inflammatory arthritis
Debilitating disease
Immunosuppression – HIV or immunosuppressive drugs
Sickle cell disease
Prosthetic material
RISK FACTORS FOR OSTEOMYELITIS ARE THE SAME AS THOSE FOR SEPTIC ARTHRITIS
What would you see on x-ray of Ankylosing spondylitis, at later stages of the disease?
Bamboo spine
calcification of all the ligaments of the spine
squaring of the vertebral bodies
subchondral sclerosis
Syndesmophytes - bony outgrowths from the spinal ligaments as they attach to adjacent vertebral bodies
fusion of joints (facet / sacroiliac / costovertebral)
