Friday 30 November 2012

Glucose-6-phosphate dehydrogenase deficiency

Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme that reduces oxidative stress by reducing glutathione levels within red cells. G6PD deficiency is an X-linked disorder common in West Africa, southern Europe, the Middle East and south-east Asia. Patients are usually asymptomatic until oxidative stress causes haemolytic anaemia. Common triggers include fava broad beans (broad-bean induced haemolysis is termed favism), drugs (including antimalarials and sulphonamide antibiotics) and infections. Treatment is supportive, although transfusions may be required for acute haemolytic crises. Heinz bodies are denatured haemoglobin aggregates that are found in the cytoplasm of red blood cells. They result from oxidant stress (e.g. G6PD deficiency) or haemolysis. Recessive carriers of the G6PD mutation are protected against malaria.

Thursday 29 November 2012

Infectious mononucleosis

Infectious mononucleosis (glandular fever) is caused by Epstein-Barr virus (EBV). Symptoms are varied and include fever, malaise, pharyngitis, tonsillitis, and lymphadenopathy. Other features are petechiae on the soft palate, jaundice, hepatomegaly and splenomegaly. Symptoms may persist for as long as 3 months.

Infectious mononucleosis is diagnosed by finding atypical lymphocytes on the blood film or by demonstrating the presence of heterophile antibodies (i.e. antibodies that agglutinate sheep or horse erythrocytes, but that are not absorbed  by guinea-pig kidney extracts!).

This is known as the monospot test or the Paul Bunnell test. Treatment is symptomatic.

In this case, the GP incorrectly prescribed antibiotics. Administration of ampicillin or amoxicillin in infectious mononucleosis causes widespread maculopapular rash. This makes treatment of any form of tonsillitis or pharyngitis with these antibiotics difficult, as EBV cannot be ruled out clinically. Penicillin is difficult to administer due to its bitter taste, although it is better to use this than potentially to cause a drug reaction with amoxicillin or ampicillin.

Wednesday 28 November 2012

Kwashiorkor

Kwashiorkor is a clinical diagnosis. It is caused by severe protein deficiency due to poor nutrition - specifically protein-calorie malnutrition. There is often adequate calorie intake but inadequate protein in the diet. Kwashiorkor is therefore more common in developing countries where carbohydrates are the staple diet. Oedema often masks the poor weight gain. Clinical features are chronic diarrhoea, irritability, listlessness, apathy, and anorexia. Classically, these children have sparse discoloured hair, are oedematous, have tight skin and have abdominal distension. Marasmus is caused by total calorie malnutrition and does not cause oedema. Children with marasmus look emaciated and do not demonstrate abdominal distension.

Kwashiorkor, from Ghanaian = displaced child - so-called as it affects children who have newly been displaced form breastfeeding.

Marasmus, from Greek marasmos = waste away, decay

Tuesday 27 November 2012

Incomplete miscarriage

Miscarriage is the most common complication of pregnancy. It is defined as the loss of pregnancy before 24 weeks. Underlying causes and risk factors of miscarriage include fetal abnormality (50%), infection ('TORCH'), increasing maternal age, maternal illness (diabetes, renal disease), abnormal uterine cavity (intrauterine contraceptive device insertion, congenital septum), antiphospholipid syndrome and intervention (amniocentesis and chorionic villus sampling). Note that exercise, intercourse and emotional trauma do not cause miscarriage. Investigation into the underlying cause of miscarriage is performed only if three miscarriages have occured.

In incomplete miscarriage, some of the fetal material has passed, but some products of conception are retained in the uterus (these are visible on ultrasound scanning). The cervical os remains open until all the products have passed (whether that be spontanous, or with medical or surgical assistance). A complete miscarriage is when the mother has experienced bleeding, all the fetal tissue has passed, there are no products of conception on scanning and the cervical os is closed. In these cases, patients do not require further hospital follow-up.

A threatened miscarriage is when there is bleeding before 24 weeks, but the fetus is still alive and the cervical os is closed on examination. Only 25% of threatened miscarriages eventually miscarry.

An inevitable miscarriage describes a scenario where there is bleeding before 24 weeks and the cervical os is dilated. The fetus may still be alive but the miscarriage will occur.

Finally, a missed miscarriaged (also known as a delayed or silent miscarriage) is when the fetus dies in utero and the cervix stays closed. There may or may not be bleeding in this case.

Monday 26 November 2012

Gynaecological malignancies

Vulva
  • Lichen sclerosis is an autoimmune loss of vulval collagen, leading to a thin epithelium. It is commonest in postmenopausal women. Affected lesions appear shiny, white and tight, and may be itchy or painful. Areas of lichen sclerosis should be biopsied, as there is a 5% risk of progression to vulval intraepithelial neoplasia (VIN) and eventually vulval squamous cell carcinoma. VIN has less malignant potential than CIN, so lesions tend to undergo observation. The exception is symptomatic VIN3, which is treated with laser therapy or topical chemotherapy
  • Vulval cancer accounts for 5% of gynaecological cancers, with a wide presenting age range. 90% are squamous carcinomas, with rarer forms including Bartholin's gland adenocarcinomas and Paget's disease of the vulva
  • Vulval carcinomas can present with pruritus, bleeding, pain/dyspareunia or a mass. Lesions spear slowly to local tissues with lymphatic spread to femoral nodes. Treatment varies from wide local excision to radical vulvectomy with bilateral node dissection. Local or systemic chemotherapy may also be effective

Ovarian
  • Ovarian cancer is the commonest cause of gynaecological cancer death in westernised society. This is mainly due to its late, and often advanced presentation and no current population screening. Endometrial cancer is the commonest malignancy of the female genital tract.

Cervical
  • There has been a recent rise in the incidence of cervical cancer among younger females. Some people blame increased promiscuity and thus more widespread infection with human papillomavirus, for this change. The younger age group has a worse prognosis.

Endometrial
  • Endometrial tumours are oestrogen dependent - hence many risk factors involve unopposed oestrogen exposure. Risk factors include not using exogenous oestrogen, obesity, nulliparity, late menopause, diabetes and pelvic irradiation for cervical cancer.

Fallopian tube
  • Fallopian tube cancer is rare, accounting for <0.3% of gynaecological cancers
  • Intermittent colicky pain settling with sudden vaginal discharge of watery fluid
  • Spread is local, via the peritoneum and lymphatics, and with metastases being present in around 50% of cases
  • The treatment options are much the same as for ovarian cancer

Sunday 25 November 2012

Sigmoid volvulus

Sigmoid volvulus occurs when the bowel twists on its mesentery, which can produce severe, rapid, strangulated obstruction. There is a characteristic AXR with an 'inverted U' loop of bowel that looks a bit like a coffee bean. It tends to occur in the elderly, constipated and co-morbid patient, and is often managed by sigmoidoscopy and insertion of a flatus tube. Sigmoid colectomy is sometimes required.
If not treated successfully, it can progress to perforation and fatal peritonitis.

Saturday 24 November 2012

Patterns of presentation of arthritis

Monoarthritis
  • Septic arthritis
  • Crystal arthritis (gout, CPPD)
  • Osteoarthritis
  • Trauma e.g. haemarthrosis

Oligoarthritis (< or = 5 joints)
  • Crystal arthritis
  • Psoriatic arthritis
  • Reactive arthritis (eg. Yersinia, Salmonella, Campylobacter)
  • Ankylosing spondylitis
  • Osteoarthritis

Polyarthritis (>5 joints involved)
  • Symmetrical
    • Rheumatoid arthritis
    • Osteoarthritis
    • Viruses (e.g. hepatitis A, B and C; mumps)
    • Systemic conditions
  • Asymmetrical
    • Reactive arthritis
    • Psoriatic arthritis
    • Systemic conditions



ALWAYS EXCLUDE SEPTIC ARTHRITIS IN ANY ACUTELY INFLAMED JOINT, AS IT CAN DESTROY A JOINT IN UNDER 24 hours. INFLAMMATION MAY BE LESS OVERT IF IMMUNOCOMPROMISED (e.g. STEROIDS) or if there is underlying joint disease. JOINT ASPIRATION IS THE KEY INVESTIGATION, AND IF YOU ARE UNABLE TO DO IT, FIND SOMEONE WHO CAN.

HOWEVER, IF YOU GO AND ASPIRATE IN A FRACTURE YOU TURN AN OPEN FRACTURE TO FRACTURE.

Friday 23 November 2012

Protein-losing enteropathy

Increased protein loss across an abnormal intestinal mucosa occasionally leads to  hypoalbuminaemia and oedema. Causes include Crohn's disease, Menetrier's disease (thickening and enlargement of gastric folds), coeliac disease and lymphatic disorders, e.g. lymphangiectasia

Thursday 22 November 2012

Shigellosis (bacillary dysentery)

Shigellosis is an acute self-limiting intestinal infection which occurs world-wide but is more common in tropical countries and in areas of poor hygiene. Transmission is by the faecal-oral route. The four Shigella species (S.dysenteriae, S.flexneri, S.boydii, and S.sonnei) invade and damage the intestinal mucosa. SOme strains of S.dysenteriae secrete a cytotoxin which results in diarrhoea. Differential diagnosis is from other causes of bloody diarrhoea. Sigmoidoscopic appearances may be the same as those in inflammatory bowel disease. Ciprofloxacin 500mg orally twice daily is the treatment of choice.

Wednesday 21 November 2012

Infection in pregnancy

Rubella (German Measles)

  • Viral infection person-to-person contact
  • MMR vaccine makes it rare now
  • 80% fetal infection first trimester, and 25% at end of third trimester
  • Maternal rubella infection causes sensorineural deafness, cataracts, congenital heart disease, learning difficulties, hepatosplenomegaly and microcephaly

Salmonella spp.
  • Gram-negative bacterium in raw or partially cooked eggs, raw meat and chicken
  • Pregnancy increases incidence and severity
  • Gastroenteritis
  • Fetus is okay

Listeria
  • Gram-positive coccus Listeria monocytogenes
  • Found in soil, animal faeces, pate and unpasteurized dairy products such as soft cheese
  • Incidence and severity of infection increased in pregnancy
  • Fever, headache, malaise, backache, abdominal pain, pharyngitis, and conjunctivitis
  • Blood cultures or placental neonatal swabs diagnostic
  • High-dose penicillin treats
  • During pregnancy can lead to miscarriage, stillbirth, preterm delivery and neonatal listeriosis, which carries a 50% mortality rate

Group B streptococci
  • 1/4 of women have group B streptococcal vaginal colonization at some stage of their pregnancy
  • Asymptomatic to mother and generally only picked up on vaginal swabs taken for other reasons
  • 1/65 neonatal deaths by causing overwhelming neotatal infection
  • Antibiotics given in labour to reduce neonatal infection risk
  • No screening programme in place at the moment

Chickenpox
  • Caused by varicella-zoster virus (human herpesvirus 3), is spread via the airborne route
  • It affects 3/1000 pregnancies
  • 90% women immune due to previous infections
  • Prodromal malaise and fever, followed by itchy vesicular rash
  • Sequelae of maternal infection are more serious in pregnant women, with 10% risk of pneumonia and 1% mortality rate
  • Diagnosis is clinical and treatment is supportive, with advice to avoid other pregnant women
  • Fetal varicella syndrome if before 16 weeks: dermatomal skin scarring, neurological defects, limb hypoplasia and eye defects

Toxoplasmosis
  • Toxoplasma gondii is a parasite that comes from unwashed fruit and vegetables, raw/cured/poorly cooked meat, unpasteurized goats' milk, or contamination from soil or cat faeces
  • The incidence is 2 in 1000 pregnancies
  • 30% of women are immune due to previous infection
  • It is rare for mothers to display clinical features, although some develop flu-like symptoms
  • Treatment is with spiramycin
  • Fetal infection occurs in 40% of cases, with the majority occurring at higher gestations (severity is greatest at lower gestations)
  • Fetal effects of toxoplasmal infection are miscarriage, stillbirth, hydrocephalus, deafness and blindness. Fetal infection can be diagnosed by amniocentesis or cordocentesis

Cytomegalovirus
  • Cytomegalovirus affects 3 in 1000 live births
  • Urine, saliva, and other bodily products
  • Maternal infection is usually asymptomatic, after a 3 to 12 week incubation period
  • Maternal primary infection can be confirmed by immunoglobulin M (IgM) in the blood, and maternal immunity is revealed by detecting IgG
  • There is no treatment and therefore no benefit to screening
  • Fetal infection diagnosed by amniocentesis or cordocentesis
  • 10-15% infected fetuses developed symptoms
  • 80% develop symptoms later in life - learning difficulties, visual impairment, progressive hearing loss or psychomotor retardation, 10-20% showing signs of infection at birth (hydrops, intrauterine growth restriction, microcephaly, hydrocephalus, hepatosplenomegaly and thrombocytopenia)

Parvovirus B19
  • Spread by respiratory droplets
  • Outbreaks in schools and manifests in children as erythema infectiosum - a 'slapped-cheek' appearance
  • Also known as 5th's disease
  • Fetal death in 9%
  • Second trimester holds highest risk of fetal infection
  • Fetal sequelae are non-immune hydrops due to chronic haemolytic anaemia and myocarditis
  • In utero blood transfusion of hydropic fetuses may prevent demise
  • No long term sequelae if they survive

Dengue fever

Dengue viruses (a member of the Flaviridae family) are transmitted to humans through bites of infected female Aedes aegypti mosquitoes. These are found mainly in Asia, Africa, Central and South America, where it is a common cause of fever and may be fatal. After an incubation period of 5-6 days there is an abrupt onset of fever, headache, retro-orbital pain and severe myalgia, often with a skin rash. Dengue haemorrhagic fever is a severe form with thrombocytopenia and spontaneous bleeding. The additional signs of circulatory failure (hypotension, tachycardia, poor peripheral perfusion) indicate dengue shock syndrome. Diagnosis during the acute phase is by detection of the virus (by cell culture, reverse transcription PCR) or its components (non-structural protein NS1) in the blood. Treatment is supportive particularly with adequate fluid resuscitation.

Tuesday 20 November 2012

5 stages of normal grief

DENIAL
ANGER
BARGAINING
DEPRESSION
ACCEPTANCE

Malaria

Malaria is a protozoan parasite widespread in the tropics and subtropics. Each year 500 million people are affected, with a mortality rate of 0.2%. In endemic areas mortality is principally in infants, and those who survive to adulthood acquire significant immunity. In hyperendemic areas an exaggerated immune response to repeated malarial infections leads to massive splenomegaly, anaemia, and elevated IgM levels (hyperreactive malarial splenomegaly, the tropical splenomegaly syndrome). Malaria parasites are scanty or absent in this syndrome and the disease responds to prolonged antimalarial treatment.


Aetiology
  • Malaria is transmitted by the bites of infected female anopheline mosquitoes.
  • Occasionally it is transmitted in contaminated blood (transfusions, contaminated equipment, injecting drug users sharing needles).
  • Rarely the parasite transmitted by importation of infected mosquitoes by air (airport malaria).
  • Four malaria parasites infect humans; by far the most hazardous is plasmodium falciparum, and the symptoms of infection with this virus can rapidly progress from an acute fever with rigors to severe multiorgan failure, coma and death
  • Once successfully treated this form does not relapse
  • The other malaria parasites are P.vivax, P.ovale and P.malariae
  • These may relapse though

Pathogenesis
  • The infective form of the parasite (sporozoites) passes through the skin and via the bloodstream to the liver.
  • Here they multiply inside hepatocytes as merozoites.
  • After a few days the infected hepatocytes rupture, releasing merozoites into the blood where they are taken up by erythrocytes and pass through further stages of development, which terminate with the rupture of the red cell
  • Rupture of red blood cells contributes to anaemia and releases pyrogens, causing fever
  • Red blood cells infected with P.falciparum adhere to the endothelium of small vessels and the consequent vascular occlusion causes severe organ damage, chiefly in the gut, kidney, liver and brain
  • P.ovale and P.vivax remain latent in the liver, and this is responsible for the relapses that may occur

Clinical features
  • The incubation period varies:
    • 10 to 14 days in P.vivax, P.ovale and P.falciparum infection
    • 18 days to 6 weeks in P.malariae infection
  • The onset of new symptoms may be delayed up to three months and 1 year in vivax malaria in the partially immune or after prophylaxis
  • There is an abrupt onset of fever (>40 degrees celcius), tachycardia and rigors, followed by profuse sweating some hours later. This may be accompanied by anaemia and hepatosplenomegaly
  • P.falciparum infection is a medical emergency because patients may deteriorate rapidly. The following clinical forms are recognised and are more likely to occur when more than 1% of the red blood cells (RBCs) are parasitized:
    • Cerebral malaria - diminished consciousness, confusion, convulsions, coma and eventually death. Hypoglycaemia, a complication of severe malaria, may present in a similar way and must be excluded
    • Blackwater fever - dark brown-black urine (haemoglobinuria) resulting from severe intravascular haemolysis


Investigations
  • The conventional method for diagnosing malaria is light microscopy of a Giemsa-stained thick and thin blood smear. Thick smears are most useful for diagnosis of malaria and thin smears are quantification of the percentage of parasitized red cells and for species identification
  • Three smears should be taken over 48 hours before the diagnosis of malaria is ruled out. Rapid antigen tests are available for near-patient use
  • Full blood count, serum urea and electrolytes, liver biochemistry and blood glucose are checked in falciparum malaria to detect complications


Management
  • Parasitological testing and confirmation of the diagnosis should be performed before antimalarial treatment is started except in remote rural areas
  • Treatment of uncomplicated malaria
    • Symptomatic malaria without signs of severity or evidence (clinical or laboratory) of vital organ dysfunction and parasite count <2%
    • Artemisinin-based combination therapies (ACT) are the recommended treatments for uncomplicated P.falciparum malaria and for the treatment of P.vivax from chloroquine-resistant areas (Indonesia, Papua New Guinea, Timor Leste and other parts of Oceania)
    • Fixed-dose combinations are preferred to the loose individual medicines co-dispensed
    • Antipyretics such as aspirin and paracetamol are given as necessary, and intravenous fluids may be required to combat dehydration and shock
  • Severe falciparum malaria
    • Is a medical emergency
    • Optimal management may require admission to the intensive care unit (ITU). Expert advice should be sought from a malaria reference centre.
      • Parenteral artesunate 2.4 mg/kg body weight i.v. or i.m given at diagnosis and then at 12 hours and 24 hours, then once a day until patient able to tolerate oral medication and complete treatment by a course of an ACT
      • Quinine if artesunate is unavailable. Quinine 20mg/kg loading dose in 5% dextrose intravenously over 4 hours, then 10mg/kg over 4 hours every 8 hours plus oral doxycycline 200 mg daily for 7 days.
      • Omit loading dose if patient taking quinine or mefloquine already as prophylaxis
      • Treatment can be switched to oral quinine when patient is stable and responding to treatment
      • Rectal artesunate is given in remote rural areas of some countries (Africa and Asia) to patients with suspected severe malaria before referral to a health facility for definitive treatment. Intramuscular artesunate or quinine are also used in this setting
  • Intravenous glucose is given for hypoglycaemia and benzodiazepines for seizures. Early dialysis for acute kidney injury should be commenced and positive-pressure ventilation for non-cardiogenic pulmonary oedema

Prevention and control
  • Effective prevention of malaria includes the following elements (ABC):
    • AWARENESS OF RISK
    • BITE AVOIDANCE - using mosquito repellants, covering up with permethrin-impregnated clothing, sleeping under impregnated bednets
    • Chemoprophylaxis
  • As a result of changing patterns of resistance, advice about chemoprophylaxis should be sought before leaving for a malaria-endemic area
  • Prophylaxis does NOT afford full protection
  • Drug regimens must start for at least 1 week before departure and continued without interruption for 4 weeks after return 
  • The rationale for this advice is to ensure therapeutic drug levels before travelling and to enable unwanted effects to be dealt with before departure
  • THe continued use of drugs after returning home will deal with infection contracted on the last day of exposure. With the now widespread geographical prevalence of chloroquine resistant P.falciparum, mefloquine (250mg weekly) is for many travellers the mainstay of malarial chemoprophylaxis
  • Malarone (proguanil/atovaquone) or doxycycline are alternatives to mefloquine

Monday 19 November 2012

Pyrexia of Unknown Origin

Pyrexia (or fever) of unknown origin (PUO) is defined as 'a documented fever persisting for >2 weeks, with no clear diagnosis despite intelligent and intensive investigation'. Occult infection remains the most common cause in adults.


Investigations

  • A detailed history and examination is essential, and the examination should be repeated on a regular basis in case new signs appear. First-line investigations are usually repeated as results may have changed since the tests were first performed:
    • Full blood count, including a differential WCC and blood film
    • ESR and CRP
    • Serum urea and electrolytes, liver biochemistry and blood glucose
    • Blood cultures - several sets from different sites at different times
    • Microscopy and culture of urine, sputum and faeces
    • Baseline serum for virology
    • Chest X-ray
    • Serum rheumatoid factor and antinuclear antibody
  • Second-line investigations are performed in conditions that remain undiagnosed and when repeat physical examination is unhelpful:
    • Abdominal imaging with ultrasound, CT or MRI to detect occult abscesses and malignancy
    • Echocardiography for infective endocarditis
    • Biopsy of liver and bone marrow occasionally; temporal artery biopsy should be considered in the elderly
    • Determination of HIV status (after counselling)

Management
  • THe treatment is of the underlying disease
  • Blind antibiotic therapy should not be given unless the patient is very unwell. In a few patients no diagnosis is reached after thorough investigations and in most of these the fever will resolve on follow-up

Causes
  • Infection (20-40%)
    • Pyogenic abscess, e.g. liver, pelvic, subphrenic
    • Tuberculosis
    • Infective endocarditis
    • Toxoplasmosis
    • Viruses: Epstein-Barr, cytomegalovirus
    • Primary human immunodeficiency virus (HIV) infection
    • Brucellosis
    • Lyme disease
  • Malignant disease (10-30%)
    • Lymphoma
    • Leukaemia
    • Renal cell carcinoma
    • Hepatocellular carcinoma
  • Vasculitides (15-20%)
    • Adult Still's disease
    • Rheumatoid arthritis
    • Systemic lupus erythematosus
    • Wegener's granulomatosis
    • Giant cell arteritis
    • Polymyalgia rheumatica
  • Miscellaneous (10-25%)
    • Drug fevers
    • Thyrotoxicosis
    • Inflammatory bowel disease
    • Sarcoidosis
    • Granulomatous hepatitis, e.g. tuberculosis, sarcoidosis
    • Factitious fever (switching thermometers, injection of pyogenic material)
    • Familial Mediterranean fever
  • Undiagnosed (5-25%)

Sunday 18 November 2012

Leptospirosis

This zoonosis is caused by a Gram-negative organism, Leptospira interrogans, which is excreted in animal urine and enters the host through a skin abrasion or intact mucous membranes. Individuals who work with animals or take part in water sports which bring them in close contact with rodents (e.g. boating lakes, diving) are most at risk.


Clinical features
  • Following an incubation period of about 10 days, the intiial leptospiraemic phase is characterised by fever, headache, malaise and myalgia, followed by an immune phase, which is most commonly manifest by meningism. Most recover uneventfully at this stage. A small proportion go on to develop hepatic and renal failure, haemolytic anaemia, and circulatory collapse (Weil's disease).

Investigations
  • Blood or CSF culture can identify the organisms in the first week of the disease. The organism may be detected in the ruine during the second week. Serology will show specific IgM antibodies by the end of the first week.

Management
  • Oral doxycycline is given for mild disease and intravenous penicillin or erythromycin for more severe disease. The complications of the disease should be treated appropriately.

Saturday 17 November 2012

Hypermagnesaemia

Hypermagnesaemia is rare and is usually iatrogenic, occurring in patients with renal failure who have been given magnesium-containing laxatives or antacids. Symptoms include neurological and cardiovascular depression, with narcosis, respiratory depression and cardiac conduction defects. The only treatment usually necessary is to stop magnesium treatment. In severe cases, intravenous calcium gluconate may be necessary to reverse the cellular toxic effects of magnesium and dextrose/insulin (as for hyperkalaemia) to lower the plasma magnesium level

Friday 16 November 2012

Hypomagnesaemia

Aetiology
  • Low serum magnesium is most often caused by loss of magnesium from the gut or kidney
  • Gastrointestinal causes include severe diarrhoea, malabsorption, extensive bowel resection and intestinal fistulae
  • Excessive renal loss of magnesium occurs with diuretics, alcohol abuse, and with an osmotic diuresis such as glycosuria in diabetes mellitus

Clinical features
  • Hypomagnesaemia increases renal excretion of potassium, inhibits secretion of parathyroid hormone and leads to parathyroid hormone resistance
  • Many of the symptoms of hypomagnesaemia are therefore due to hypokalaemia and hypocalcaemia


Management
  • The underlying cause must be corrected where possible and oral supplements given (magnesium chloride 5-20 mmol daily or magnesium oxide tablets 600mg four times daily)
  • Symptomatic severe magnesium deficiency should be treated by intravenous infusion (40 mmol of MgCl in 100 mL of sodium chloride 0.9% or dextrose 5% over 2 hours), plus a loading dose (8 mmol over 10-15 minutes) if there are seizures or ventricular arrhythmias
  • Take care when interpreting repeat serum concentrations after treatment - the extracellular values may appear to normalize quickly while the intracellular concentration requires longer to replenish (may require up to 160 mmol over 5 days to correct)

Thursday 15 November 2012

Antiviral therapies

Herpes Zoster Infection
  • Oral aciclovir


Cytomegalovirus (CMV)
  • 'Mozarrella and tomato pizza' appearance
  • Risk of blindness, HIV patients, medical emergency
  • Intravenous Ganciclovir
  • Foscarnet is also used 

Severe Respiratory Syncytial Virus (RSV) bronchiolitis
  • Inhaled ribavirin
  • Monoclonal antibody is now available that can be used to prevent RSV infection in infants at high risk (palivizumab)

Chronic hepatitis-C infection
  • Interferon-alpha given by subcutaneous injection
  • Combination therapy with ribavirin is more effective and should be continued for 6 months

HIV
  • TWO NUCLEOSIDE ANALOGUE REVERSE TRANSCRIPTASE INHIBITORS (AZT and didanosine)
  • ONE PROTEASE INHIBITOR (Indinavir)
  • Zidovudine + Didanosine
  • Indinavir

Wednesday 14 November 2012

Treatment of infection

Scabies
  • Itching digital web spaces
  • Topical malathion

Invasive aspergillosis
  • Intravenous/liposomal amphotericin
  • Amphotericin has renal toxicity
  • Disturbances in renal function can lead to hypokalaemia (causing arrhythmias) and hypomagnesia

Vulvovaginal candidiasis
  • Thrush
  • Topical use of azole pessaries/creams
  • Oral fluconazole can be given

Fungal toenail infections
  • Terbinafine
  • Not azoles because they are CYP450 enzyme inhibitors

Pneumocystis carinii pneumonia
  • Co-trimoxazole is combination of one part trimethoprim to five parts sulfamethoxazole
  • Stevens-Johnson syndrome and blood dyscrasias -> Sulphonamide component

Tuesday 13 November 2012

Antibiotics

Trichomonas Vaginalis
  • Metronidazole
  • Sexually transmitted
  • Vaginitis in women and non-gonococcal urethritis in men
  • Treat patient and partner

Severe community-acquired pneumonia
  • Cefuroxime + Erythromycin
  • Intravenous combination of a broad-spectrum Beta-lactamase antibiotic together with a macrolide

Salmonella infection
  • Ciprofloxacin
  • Especially if patient is systemically unwell

Meningococcal (Neisseria meningitidis)
  • IV benzylpenicillin

Impetigo
  • Flucloxacillin if Staphylococcus aureus
  • Weeping, exudative area with characteristic honey-coloured crusting on the surface
  • Topical fusidic acid can be used for small areas but flucloxacillin if widespread areas

Monday 12 November 2012

Antibiotics

Septic arthritis
  • Medical emergency
  • Urgent gram staining and culture are indicated
  • Staphylococcus aureus is the most common infecting pathogen
  • Intravenous benzylpenicillin plus flucloxacillin
  • Opportunistic infection if the patient is immunocompromised (e.g. HIV positive)

Systemic MRSA infection
  • Vancomycin is a glycopeptide antibiotic indicated for treatment of MRSA infection
  • Should be given intravenously for systemic infection
  • Teicoplanin is similar glycopeptide antibiotic with longer duration of action (so it can be given once daily)

Uncomplicated UTI
  • Trimethoprim should not be given in pregnancy because it is a folic acid antagonist and teratogenic
  • Quinolones and tetracycline should be avoided.
  • Adverse effects of nitrofurantoin include diarrhoea, vomiting, neuropathy, and fibrosis
  • Nitrofurantoin should be avoided in pregnant mothers at term and in breast feeding mothers

Antibiotic prophylaxis for cholecystectomy
  • Intravenous co-amoxiclav is alternative to intravenous cefuroxime plus metronidazole

Chlamydia infection
  • Tetracycline is first-line treatment for chlamydia infection
  • Absolutely contraindicated in pregnancy and when breast-feeding
  • Tetracyclines are deposited in growing bone and can lead to permanent staining of teeth and dental hypoplasia
  • Patients treated with tetracycline are told to avoid milk products because these decrease absorption of the drug

Saturday 10 November 2012

Hypercalcaemia

Myeloma
  • Even in the absence of the IgG chains in the urine, there are certain red flags that suggest a sinister cause for the back pain, e.g. weight loss and elevated ESR
  • More than 1 g light chains excreted in the urine per day is a major criterion for the diagnosis of myeloma
  • Bisphosphonates may be used to treat hypercalcaemia associated with myeloma
  • Radiotherapy can be used to relieve bone pain

Sarcoidosis
  • Dry cough, shortness of breath, bilateral hilar lymphadenopathy
  • Abnormal incidental chest radiograph finding or respiratory symptoms are the initial presentations in up to 50% of sarcoid patients
  • TB, malignancy, silicosis and extrinsic allergic alveolitis are other causes of bilateral hilar lymphadenopathy
  • There is a higher incidence of sarcoidosis among African-Carribeans

Bone metastases
  • Non-steroidal anti-inflammatory drugs [NSAIDs] such as ibuprofen are a particularly good first-line drug for the treatment of bone pain associated with metastases

PTH-like hormone secretion
  • Ectopic parathyroid hormone (PTH)-related protein secretion by squamous cell carcinoma is a relatively rare cause of hypercalcaemia

Tertiary hyperparathyroidism
  • Tertiary hyperparathyroidism involves the development of autonomous parathyroid hyperplasia that occurs after long-standing secondary hyper-parathyroidism
  • Both plasma calcium and phosphate are raised
  • Secondary hyperparathyroidism is physiological hypertrophy of the parathyroid glands in response to hypocalcaemia
  • In this way, plasma calcium is usually low or normal in secondary hyperparathyroidism
  • Vitamin D deficiency and chronic renal failure are well-recognised causes of secondary hyperparathyroidism

Friday 9 November 2012

Ulcers

Venous ulcers

  • Found around the lower third of the leg
  • Long-standing venous ulcer may be malignant change to form a squamous cell carcinoma - Marjolin's ulcer

Basal cell carcinoma
  • Basal cell carcinoma (also known as a rodent ulcer) is a locally invasive carcinoma that is more common areas of sun-exposed skin
  • The carcinoma starts as a slow-growing nodule that may be itchy or sometimes bleeds
  • There is necrosis of the centre, leaving a rolled edge
  • Basal cell carcinoma does not metastasise and surrounding lymph nodes should not enlarge

Squamous cell carcinoma
  • Bleeding is more common in squamous cell carcinoma than in basal cell carcinoma
  • Enlarged lymph nodes may be present because it does metastasise
  • Squamous cell carcinoma has a classic everted edge

Ischaemic ulcers
  • Excruciatingly painful
  • Changes to overlying dressing can be painful for several hours
  • Ischaemic ulcers are characteristically deeper than venous ulcers and can penetrate down to the bone
  • Surrounding area is cold as a result of ischaemia

Neuropathic ulcer
  • Occur as a result of impaired sensation caused by neurological deficit of whatever cause
  • Diabetes mellitus is the most common cause of neuropathic ulcers
  • Characteristically painless

Anorectal conditions

Fistula in ano

  • Fistulae are well-recognised complication of Crohn's disease
  • Full rectal examination is important to detect other causes of fistula in ano e.g. rectal carcinoma

Fissure in ano
  • Very painful, rectal examination not possible
  • Constipated because defecation is so painful
  • Vicious cycle as the stools become harder, resulting in defecation becoming more difficult and painful

Pilinoidal sinus
  • Always occur in the midline of the natal cleft
  • More common in men than in women

Haemorrhoids
  • Spongy vascular tissue surrounds and helps close the anal canal
  • If they cushions enlarge they can prolapse and bleed to form haemorrhoids/piles
  • First-degree haemorrhoids remain in the rectum
  • Second-degree haemorrhoids prolapse through the rectum on defecation but spontaneously reduce
  • Third-degree haemorrhoids remain prolapsed
  • Constipation, need high fibre diet

Perianal warts
  • Human papilloma virus (HPV) infection is responsible for anogenital warts and is particularly associated with unprotected sexual contact
  • Look out for the appearance of such lesions in immunocompromised individuals
  • HPV-related warts are referred to as condylomata acuminata
  • Condyloma lata are broad-based, flat-topped and necrotic papules that occur with secondary syphilis
  • Condyloma lata must be differentiated from condylomata acuminata (biopsy?)

Pain/lumps in the scrotum

Seminoma

  • Seminoma usually presents between the age of 30 to 40 years whereas teratoma commonly presents earlier (20-30 years). Undescended testes are an important risk factor for testicular tumours

Torsion of the testes
  • Congenital abnormality ('bell clapper deformity') that allows torsion of the whole testicle
  • Normally, it is fixed within the tunica vaginalis
  • Pain of torsion is severe and often associated with nausea and vomiting
  • History of trauma (but doesn't need history of trauma)
  • Acute epididymo-orchitis similar presentation
  • Explore surgically to rule out torsion if there is any doubt

Hydrocoele
  • Fluid of hydrocoele surrounds body of testis, and therefore underlying testis is impalpable
  • Primary hydrocoele is idiopathic
  • Secondary hydrocoele is secondary to trauma, tumour, or infection
  • Epididymal cyst is separate from the testis and therefore the testis is impalpable

Acute epididymo-orchitis
  • UTI symptoms such as Frequency and Dysuria
  • Unprotected sexual intercourse
  • Similar to torsion of the testes

Thursday 8 November 2012

Erythema Nodosum and Erythema Multiforme

Erythema Nodosum
  • Streptococcal infection
  • Drugs (e.g. antibiotics, oral contraceptive pill)
  • Tuberculosis
  • Inflammatory bowel disease
  • Sarcoid
  • Leprosy
  • Yersinia infection
  • Fungal infection e.g. histoplasmosis
  • Chlamydia infection
  • Idiopathic

Erythema Multiforme
  • Herpes/Epstein-Barr virus infection
  • Drugs (e.g. antibiotics, barbiturates)
  • Mycoplasma infections
  • Connective tissue disease, e.g. SLE
  • HIV
  • Carcinoma/lymphoma

Wednesday 7 November 2012

Post-exposure prophylaxis of HIV

Post-needlestick injury
  • Blood from patient and injured person

Then 4-6 weeks of
  • Zidovudine
    • Inhibits HIV virus' reverse transcription rendering it unable to make cDNA
  • Lamivudine
    • Same, but works not only on types 1 and 2 but also of Hepatitis B
  • +/- Indinavir
    • Protease inhibitor, rendering virus unable to create final viral protein through cleavage

Tuesday 6 November 2012

Glomerulonephritis

Proliferative glomerulonephritis
  • Diffuse
    • Post-streptococcal
      • Acute nephritic syndrome
  • Focal segmental
    • Henoch-Schonlein purpura
      • Proteinuria
    • SLE 
      • Haematuria
  • Crescentic
    • Wegener's granulomatosis
      • Progressive renal failure
    • Goodpasture's syndrome

Mesangiocapillary
  • Type 1
    • Hepatitis B and C
      • Haematuria
      • Proteinuria
  • Type 2
    • Measles
      • Nephrotic syndrome

Membranous
  • Unknown
    • Nephrotic syndrome
  • Malaria
  • Minimal change
    • Unknown
      • Nephrotic syndrome (especially in children)
  • IgA nephropathy
    • Henoch-Schonlein purpura
      • Asymptomatic haematuria
  • Focal glomerulosclerosis
    • Diabetes mellitus
      • Proteinuria
      • Nephrotic syndrome

Monday 5 November 2012

Acute Pulmonary Oedema

Clinical features
  • Extreme breathlessness (often n middle of night)
  • Wheeze
  • Anxiety
  • Cold sweat
  • Cough with frothy pink sputum
  • Grey and/or cyanosed
  • Tachypnoea
  • Peripherally shut down and cold
  • Raised JVP
  • Gallop rhythm
  • Crackles and wheeze throughout chest
  • Hypotension

Immediate investigations
  • Chest X-ray - exclude pneumothorax
  • Arterial blood gases - low PO2, +- high PCO2
  • ECG - arrhythmia

Immediate management
  • Sit up
  • High-flow oxygen
  • I.v. furosemide (frusemide) 40-80 mg
  • I.v. diamorphine 2.5-5mg (not if BP < 80 systolic)
  • I.v. metoclopramide 10 mg
  • I.v. GTN (if not hypotensive)
  • Nebulised salbutamol 2.5 mg if bronchospasm

Friday 2 November 2012

Common dissociative/conversion symptoms

Dissociative (mental)
  • Amnesia
  • Fugue
  • Pseudodementia
  • Dissociative identity disorder
  • Psychosis

Conversion (physical)
  • Paralysis
  • Gait disorder
  • Tremor
  • Aphonia
  • Mutism
  • Sensory symptoms
  • Globus hystericus
  • Hysterical fits
  • Blindness

Clinical features of anxiety

Physical
  • Gastrointestinal
    • Dry mouth
    • Dysphagia
    • Epigastric pain
    • Flatulence/aerophagy
    • Diarrhoea
  • Respiratory
    • Sensation of chest constriction
    • Difficulty inhaling
    • Over-breathing
  • Cardiovascular
    • Palpitations, awareness of missed beat
    • Chest pain
  • Genitourinary
    • Frequency
    • Failure of erection
    • Lack of libido
  • Nervous system
    • Fatigue
    • Blurred vision
    • Dizziness
    • Headache
    • Sleep disturbance


Psychological
  • Apprehension and fear
  • Irritability
  • Difficulty concentrating
  • Distractibility
  • Restlessness
  • Sensitivity to noise
  • Depression
  • Depersonalisation
  • Derealisation

Unwanted effects of drugs used in affective disorders

Tricyclic antidepressants
  • Anticholinergic effects
    • Dry mouth
    • Constipation
    • Tremor
    • Blurry vision
    • Urinary retention
    • Postural hypotension
  • Cardiac effects
    • ECG changes
    • Arrhythmias
  • Lowered seizure threshold
  • Weight gain
  • Sedation
  • Mania

Lithium
  • GI symptoms
  • Hypothyroidism
  • Fine tremor
  • Weight gain (increased appetite)
  • Polyuria/polydipsia
  • Toxic symptoms
  • Drowsiness
  • Blurred vision
  • Tremor
  • Ataxia
  • Dysarthria
  • Convulsions
  • Coma and death

Thursday 1 November 2012

The radial pulse

Low volume
  • Low BP
  • Aortic stenosis

Pulsus alternans
  • Variable volume due to cardiac failure

Pulsus paradoxus
  • Cardiac tamponade
  • Volume reduces on inspiration in acute asthma

Collapsing pulse
  • Aortic regurgitation