Oral Candidiasis and its Association with Immune System Defects

Oral candidiasis, a fungal infection in the mouth, is a concerning condition in young healthy individuals as it may indicate an underlying defect in the immune system. Further investigation is necessary to identify the root cause of the infection. In London, men who have sex with men have a high prevalence of HIV, which is a likely diagnosis in such cases. HIV weakens the immune system, making individuals more susceptible to infections and other health complications.

Apart from HIV, other immune system defects may also lead to oral candidiasis. Recurrent attacks of shingles in a young person may also indicate a weakened immune system. Additionally, HIV infection is a predisposing factor for deep vein thrombosis (DVT), a condition where blood clots form in the veins deep within the body. Therefore, it is crucial to investigate the underlying cause of oral candidiasis and other related conditions to ensure timely diagnosis and appropriate treatment.

Overall, oral candidiasis is a red flag for immune system defects, and healthcare professionals should be vigilant in identifying and addressing the root cause of the infection.

Understanding the Hierarchy of Evidence-Based Medicine

In order to determine the strength of evidence behind clinical guidelines, the Centre for Evidence-Based Medicine at the University of Oxford has established a hierarchy of evidence. At the top of the hierarchy is Level 1a evidence, which consists of systematic reviews of randomized trials. At the bottom is Level 5 evidence, which is based on expert consensus.

Case series fall under Level 3 evidence, while expert consensus using mechanism-based reasoning is classified as Level 4 evidence. The ideal for guideline recommendations is a systematic review of randomized controlled trials, which is classified as Level 1 evidence. Non-randomized cohort studies of good quality are classified under Level 2, while low-quality studies fall under Level 4.

Randomized, placebo-controlled trials with a narrow confidence interval are Level 1b evidence, while those with less than 80% follow-up are classified as Level 2b evidence. Understanding this hierarchy is crucial for making evidence-based decisions in clinical practice.

Genotypes and Associated Syndromes

There are several genotypes that can lead to different syndromes.

The genotype 46,XY can cause androgen insensitivity syndrome, where the patient is genotypically male but has complete resistance to testosterone. This results in the absence of male internal genitalia.

The genotype 46,XX is associated with a phenotypically normal female.

45,XO causes Turner syndrome, which is characterized by short stature, webbed neck, and streak gonads in girls.

47,XXY causes Klinefelter syndrome in males, which is characterized by atrophic testes, azoospermia, wide-set nipples, female distribution of body hair, and mild intellectual disability.

47,XYY causes tall stature, acne, and mild mental retardation in men. This genotype is also associated with aggressive behavior, but normal fertility.

A diagnosis of miscarriage can be made when a transvaginal ultrasound shows a crown-rump length greater than 7mm without cardiac activity. In this case, the patient has experienced a missed miscarriage, as the ultrasound revealed an intrauterine foetus of a size consistent with around 6 weeks gestation, but without heartbeat. The closed cervical os and history of spotting further support this diagnosis. A complete miscarriage, inevitable miscarriage, and partial miscarriage are not applicable in this scenario.

Miscarriage is a common complication that can occur in up to 25% of all pregnancies. There are different types of miscarriage, each with its own set of symptoms and characteristics. Threatened miscarriage is painless vaginal bleeding that occurs before 24 weeks, typically at 6-9 weeks. The bleeding is usually less than menstruation, and the cervical os is closed. Missed or delayed miscarriage is when a gestational sac containing a dead fetus is present before 20 weeks, without the symptoms of expulsion. The mother may experience light vaginal bleeding or discharge, and the symptoms of pregnancy may disappear. Pain is not usually a feature, and the cervical os is closed. Inevitable miscarriage is characterized by heavy bleeding with clots and pain, and the cervical os is open. Incomplete miscarriage occurs when not all products of conception have been expelled, and there is pain and vaginal bleeding. The cervical os is open in this type of miscarriage.

The woman experiences a sudden smell of roses while at work, but remains conscious throughout the event. This suggests that she is having a focal aware seizure, which is a type of seizure that only affects a specific area of the brain. The fact that the twitching is limited to her left arm further supports this diagnosis. It is important to note that this is different from a focal impaired awareness seizure, which would cause the patient to have reduced consciousness and confusion. Absence seizures, atonic seizures, and generalised tonic-clonic seizures are also ruled out based on the patient’s symptoms.

Epilepsy is classified based on three key features: where seizures begin in the brain, level of awareness during a seizure, and other features of seizures. Focal seizures, previously known as partial seizures, start in a specific area on one side of the brain. The level of awareness can vary in focal seizures, and they can be further classified as focal aware, focal impaired awareness, or awareness unknown. Focal seizures can also be motor, non-motor, or have other features such as aura. Generalized seizures involve networks on both sides of the brain at the onset, and consciousness is lost immediately. They can be further subdivided into motor and non-motor types. Unknown onset is used when the origin of the seizure is unknown. Focal to bilateral seizures start on one side of the brain in a specific area before spreading to both lobes and were previously known as secondary generalized seizures.

When examining acid-base imbalances in post-operative individuals, it is crucial to take into account the possible adverse effects associated with the particular surgery. In this instance, the patient has an ileostomy to facilitate the drainage of bowel contents through a stoma bag following the operation. These patients may experience substantial depletion of fluids, electrolytes, and acid-base imbalances (metabolic acidosis) if the output from the ileostomy increases or if there are changes or disruptions to their dietary intake. Therefore, it is essential to keep track of their fluid balance, including the output from the stoma, to ensure their well-being.

Colorectal cancer is typically diagnosed through CT scans and colonoscopies or CT colonography. Patients with tumors below the peritoneal reflection should also undergo MRI to evaluate their mesorectum. Once staging is complete, a treatment plan is formulated by a dedicated colorectal MDT meeting.

For colon cancer, surgery is the primary treatment option, with resectional surgery being the only cure. The procedure is tailored to the patient and tumor location, with lymphatic chains being resected based on arterial supply. Anastomosis is the preferred method of restoring continuity, but in some cases, an end stoma may be necessary. Chemotherapy is often offered to patients with risk factors for disease recurrence.

Rectal cancer management differs from colon cancer due to the rectum’s anatomical location. Tumors can be surgically resected with either an anterior resection or an abdominoperineal excision of rectum (APER). A meticulous dissection of the mesorectal fat and lymph nodes is integral to the procedure. Neoadjuvant radiotherapy is often offered to patients prior to resectional surgery, and those with obstructing rectal cancer should have a defunctioning loop colostomy.

Segmental resections based on blood supply and lymphatic drainage are the primary operations for cancer. The type of resection and anastomosis depend on the site of cancer. In emergency situations where the bowel has perforated, an end colostomy is often safer. Left-sided resections are more risky, but ileocolic anastomoses are relatively safe even in the emergency setting and do not need to be defunctioned.

Hormone Replacement Therapy (HRT) Options for Women with a History of DVT

Women with a history of deep vein thrombosis (DVT) need to be cautious when considering Hormone Replacement Therapy (HRT) options. Here are some options:

1. Transdermal Combined HRT Patches: This option is the best as it bypasses the enterohepatic circulation, reducing the effect on the hepatic clotting system.

2. Oral Continuous Combined HRT: This option is only suitable for postmenopausal women who have not had a period for over a year.

3. Oral Sequential Combined HRT: This option is suitable for perimenopausal women who are still having periods. However, oral preparations increase the risk of clots, compared to transdermal preparations.

4. Raloxifene: This is a selective oestrogen receptor modulator (SERM) that reduces osteoporosis in postmenopausal women. It has effects on lipids and bone but does not stimulate the endometrium or breast.

5. Tibolone: This synthetic steroid has oestrogenic, progestational, and androgenic properties. It is only suitable for postmenopausal women who had their last period more than a year ago.

In conclusion, women with a history of DVT should consult their healthcare provider before starting any HRT option. Transdermal combined HRT patches may be the safest option for these women.

Genetic Phenomena: Anticipation, Mosaicism, Incomplete Penetrance, Genetic Imprinting, and Translocation of a Chromosome

Genetics is a complex field that involves the study of heredity and the variation of inherited traits. Within this field, there are several genetic phenomena that can occur, each with its own unique characteristics and implications. These phenomena include anticipation, mosaicism, incomplete penetrance, genetic imprinting, and translocation of a chromosome.

Anticipation refers to inherited conditions that become more severe and have an earlier onset in subsequent generations. This is often associated with trinucleotide repeats of DNA bases, which can expand and lead to an increase in severity. Examples of disorders with anticipation include Huntington’s disease, myotonic dystrophy, and fragile X syndrome.

Mosaicism is the presence of two cell lines with different genetic compositions within the same individual. This can occur due to errors during cell division and can result in conditions such as mosaic trisomy 21.

Incomplete penetrance refers to the likelihood of a condition being present in an individual with a certain trait. Incomplete penetrance means that some people who carry a certain trait will have the condition, while others will not. Examples include the BRCA1 and BRCA2 genes, as well as RB gene mutations.

Genetic imprinting involves the silencing of one copy of an allele. This can result in conditions such as Angelman and Prader-Willi syndromes, where only one allele is expressed due to the silencing of the other.

Translocation of a chromosome refers to the exchange of genetic material between non-homologous chromosomes. This can result in conditions such as chronic myeloid leukemia, which is associated with the Philadelphia chromosome resulting from a translocation between chromosomes 9 and 22.

Understanding these genetic phenomena is crucial for the diagnosis and treatment of genetic disorders, as well as for advancing our knowledge of genetics as a whole.

Pregnant women should avoid taking ACE inhibitors like ramipril as they can lead to fetal abnormalities and renal failure. These medications are believed to hinder the production of fetal urine, resulting in oligohydramnios, and increase the likelihood of cranial and cardiac defects. However, other drugs do not pose any known risks during pregnancy and can be continued if necessary.

Angiotensin-converting enzyme (ACE) inhibitors are commonly used as the first-line treatment for hypertension and heart failure in younger patients. However, they may not be as effective in treating hypertensive Afro-Caribbean patients. These inhibitors are also used to treat diabetic nephropathy and for secondary prevention of ischaemic heart disease. The mechanism of action of ACE inhibitors is to inhibit the conversion of angiotensin I to angiotensin II. They are metabolized in the liver through phase 1 metabolism.

ACE inhibitors may cause side effects such as cough, which occurs in around 15% of patients and may occur up to a year after starting treatment. This is thought to be due to increased bradykinin levels. Angioedema may also occur up to a year after starting treatment. Hyperkalaemia and first-dose hypotension are other potential side effects, especially in patients taking diuretics. ACE inhibitors should be avoided during pregnancy and breastfeeding, and caution should be exercised in patients with renovascular disease, aortic stenosis, or hereditary or idiopathic angioedema.

Patients receiving high-dose diuretic therapy (more than 80 mg of furosemide a day) are at an increased risk of hypotension when taking ACE inhibitors. Before initiating treatment, urea and electrolytes should be checked, and after increasing the dose, a rise in creatinine and potassium may be expected. Acceptable changes include an increase in serum creatinine up to 30% from baseline and an increase in potassium up to 5.5 mmol/l. Patients with undiagnosed bilateral renal artery stenosis may experience significant renal impairment. The current NICE guidelines provide a flow chart for the management of hypertension.

Scabies: Symptoms, Causes, and Treatment

Scabies is a skin infestation that can cause lesions on the palms and soles, accompanied by intense itching. If a sibling has a similar history, it is likely that they are also infested with scabies. The lesions are caused by scratching and can become exudative. The treatment of choice for scabies is topical permethrin or malathion. These medications can help to kill the mites that cause scabies and alleviate the symptoms of itching and skin irritation.

Bendroflumethiazide, a thiazide-like diuretic, is prescribed as a third-line treatment for hypertension. However, it can increase the risk of digoxin toxicity when taken with digoxin. Symptoms of digoxin toxicity include nausea, vomiting, confusion, weakness, palpitations, and can lead to serious complications such as hyperkalaemia, arrhythmias, and cardiac arrest. Dabigatran, a direct thrombin inhibitor, is a potential medication for stroke prophylaxis in patients with atrial fibrillation, but it does not cause digoxin toxicity. Flecainide, an anti-arrhythmic agent, can cause bradycardia when taken with digoxin, but it is not likely to cause digoxin toxicity. Furosemide, a loop diuretic, is not indicated for hypertension or atrial fibrillation and is not the most likely cause of digoxin toxicity in this patient who has no signs of fluid overload.

Understanding Digoxin and Its Toxicity

Digoxin is a medication used for rate control in atrial fibrillation and for improving symptoms in heart failure patients. It works by decreasing conduction through the atrioventricular node and increasing the force of cardiac muscle contraction. However, it has a narrow therapeutic index and requires monitoring for toxicity.

Toxicity may occur even when the digoxin concentration is within the therapeutic range. Symptoms of toxicity include lethargy, nausea, vomiting, anorexia, confusion, yellow-green vision, arrhythmias, and gynaecomastia. Hypokalaemia is a classic precipitating factor, as it allows digoxin to more easily bind to the ATPase pump and increase its inhibitory effects. Other factors that may contribute to toxicity include increasing age, renal failure, myocardial ischaemia, electrolyte imbalances, hypoalbuminaemia, hypothermia, hypothyroidism, and certain medications such as amiodarone, quinidine, and verapamil.

Management of digoxin toxicity involves the use of Digibind, correction of arrhythmias, and monitoring of potassium levels. It is important to recognize the potential for toxicity and monitor patients accordingly to prevent adverse outcomes.

Tamoxifen is the preferred treatment for premenopausal women with oestrogen receptor-positive breast cancer. It is a selective oestrogen receptor modulator (SERM) that partially antagonizes the oestrogen receptor. Other options for endocrine therapy include aromatase inhibitors and GnRH agonists, but these are not typically used as first-line treatment for premenopausal women with breast cancer. GnRH antagonists and complete antagonists of the oestrogen receptor are not used in the management of breast cancer.

Anti-oestrogen drugs are used in the management of oestrogen receptor-positive breast cancer. Selective oEstrogen Receptor Modulators (SERM) such as Tamoxifen act as an oestrogen receptor antagonist and partial agonist. However, Tamoxifen can cause adverse effects such as menstrual disturbance, hot flashes, venous thromboembolism, and endometrial cancer. On the other hand, aromatase inhibitors like Anastrozole and Letrozole reduce peripheral oestrogen synthesis, which is important in postmenopausal women. Anastrozole is used for ER +ve breast cancer in this group. However, aromatase inhibitors can cause adverse effects such as osteoporosis, hot flashes, arthralgia, myalgia, and insomnia. NICE recommends a DEXA scan when initiating a patient on aromatase inhibitors for breast cancer.

Different Types of Bone Tumours and their Characteristics

Bone tumours can be classified into different types based on their characteristics. Here are some of the most common types of bone tumours and their features:

Chondrosarcoma: This is a malignant tumour that arises from cartilage. It is commonly found in long bones and is characterized by popcorn or cotton wool calcification. Paget’s disease is also associated with cotton wool calcification.

Osteoid osteoma: This is a benign, isolated lesion that is usually less than 2 cm in size and has an ovoid shape.

Osteosarcoma: This is the most common malignant bone tumour and is characterized by sun-ray spiculations and Codman’s triangle. Codman’s triangle is a triangular area of new subperiosteal bone that is created when the periosteum is raised away from the bone by an aggressive bone lesion.

Ewing’s sarcoma: This is the second most common malignant bone tumour and is characterized by onion skin periostitis and Codman’s triangle.

Osteoclastoma: This is a well-defined, non-sclerotic area that is usually not malignant.

In summary, bone tumours can have different characteristics and features, and their classification can help in their diagnosis and treatment.

Prescribing pyridoxine can help lower the risk of peripheral neuropathy associated with isoniazid.

Side-Effects and Mechanism of Action of Tuberculosis Drugs

Rifampicin is a drug that inhibits bacterial DNA dependent RNA polymerase, which prevents the transcription of DNA into mRNA. However, it is a potent liver enzyme inducer and can cause hepatitis, orange secretions, and flu-like symptoms.

Isoniazid, on the other hand, inhibits mycolic acid synthesis. It can cause peripheral neuropathy, which can be prevented with pyridoxine (Vitamin B6). It can also cause hepatitis and agranulocytosis. Additionally, it is a liver enzyme inhibitor.

Pyrazinamide is converted by pyrazinamidase into pyrazinoic acid, which in turn inhibits fatty acid synthase (FAS) I. However, it can cause hyperuricaemia, leading to gout, as well as arthralgia, myalgia, and hepatitis.

Lastly, Ethambutol inhibits the enzyme arabinosyl transferase, which polymerizes arabinose into arabinan. It can cause optic neuritis, so it is important to check visual acuity before and during treatment. Additionally, the dose needs adjusting in patients with renal impairment.

In summary, these tuberculosis drugs have different mechanisms of action and can cause various side-effects. It is important to monitor patients closely and adjust treatment accordingly to ensure the best possible outcomes.

Biliary colic is characterized by intermittent pain caused by a gallstone passing through the biliary tree. Unlike other gallstone-related conditions, such as cholecystitis, biliary colic does not cause fever or abnormal liver function tests/inflammatory markers. The absence of jaundice suggests that the stone is not obstructing the common bile duct, resulting in normal liver enzymes. Therefore, the correct answer is normal ALP and γGT, normal AST and ALT, and normal CRP. Referred pain may also be present at the tip of the scapula.

Biliary colic is a condition that occurs when gallstones pass through the biliary tree. The risk factors for this condition are commonly referred to as the ‘4 F’s’, which include being overweight, female, fertile, and over the age of forty. Other risk factors include diabetes, Crohn’s disease, rapid weight loss, and certain medications. Biliary colic occurs due to an increase in cholesterol, a decrease in bile salts, and biliary stasis. The pain associated with this condition is caused by the gallbladder contracting against a stone lodged in the cystic duct. Symptoms include right upper quadrant abdominal pain, nausea, and vomiting. Diagnosis is typically made through ultrasound. Elective laparoscopic cholecystectomy is the recommended treatment for biliary colic. However, around 15% of patients may have gallstones in the common bile duct at the time of surgery, which can result in obstructive jaundice. Other possible complications of gallstone-related disease include acute cholecystitis, ascending cholangitis, acute pancreatitis, gallstone ileus, and gallbladder cancer.

If a patient has a known allergy to a sulfa drug like co-trimoxazole, they should avoid taking sulfasalazine. However, hydroxychloroquine, leflunomide, methotrexate, and sarilumab are not contraindicated for this patient. These drugs may be considered as first-line treatments for rheumatoid arthritis, depending on the patient’s disease activity and response to other medications. It is important to note that sulfasalazine should be avoided in patients with a sulfa drug allergy.

Sulfasalazine: A DMARD for Inflammatory Arthritis and Bowel Disease

Sulfasalazine is a type of disease modifying anti-rheumatic drug (DMARD) that is commonly used to manage inflammatory arthritis, particularly rheumatoid arthritis, as well as inflammatory bowel disease. This medication is a prodrug for 5-ASA, which works by reducing neutrophil chemotaxis and suppressing the proliferation of lymphocytes and pro-inflammatory cytokines.

However, caution should be exercised when using sulfasalazine in patients with G6PD deficiency or those who are allergic to aspirin or sulphonamides due to the risk of cross-sensitivity. Adverse effects of sulfasalazine may include oligospermia, Stevens-Johnson syndrome, pneumonitis/lung fibrosis, myelosuppression, Heinz body anaemia, megaloblastic anaemia, and the potential to color tears and stain contact lenses.

Despite these potential side effects, sulfasalazine is considered safe to use during pregnancy and breastfeeding, making it a viable option for women who require treatment for inflammatory arthritis or bowel disease. Overall, sulfasalazine is an effective DMARD that can help manage the symptoms of these conditions and improve patients’ quality of life.

According to NICE guidelines for cervical cancer screening, if the first repeat smear at 12 months is still positive for high-risk human papillomavirus (hrHPV), the next step is to repeat the smear 12 months later (i.e. at 24 months). If the patient remains hrHPV positive but cytology negative at 12 months, they should have another HPV test in a further 12 months. If the patient becomes hrHPV negative at 24 months, they can return to routine recall. However, if they remain hrHPV positive, cytology negative or inadequate at 24 months, they should be referred to colposcopy.

The cervical cancer screening program has evolved to include HPV testing, which allows for further risk stratification. A negative hrHPV result means a return to normal recall, while a positive result requires cytological examination. Abnormal cytology results lead to colposcopy, while normal cytology results require a repeat test at 12 months. Inadequate samples require a repeat within 3 months, and two consecutive inadequate samples lead to colposcopy. Treatment for CIN typically involves LLETZ or cryotherapy. Individuals who have been treated for CIN should be invited for a test of cure repeat cervical sample 6 months after treatment.

Understanding Eating Disorders: Bulimia Nervosa and Anorexia Nervosa

Eating disorders are complex mental health conditions that can have serious physical and emotional consequences. Two common types of eating disorders are bulimia nervosa and anorexia nervosa.

Bulimia nervosa is characterized by episodes of binge eating, followed by purging behaviors such as vomiting, laxative abuse, or excessive exercise. People with bulimia often feel a loss of control during binge episodes and experience intense guilt afterwards. They may also engage in periods of dietary restraint and have a preoccupation with body weight and shape. Bulimia is more common in women and can cause dental problems, electrolyte imbalances, and other medical complications.

Anorexia nervosa involves deliberate weight loss to a low weight, often through restricted eating and excessive exercise. People with anorexia have a fear of gaining weight and a distorted body image, leading to a preoccupation with food and weight. Anorexia can cause severe malnutrition and medical complications such as osteoporosis, heart problems, and hormonal imbalances.

It is important to seek professional help if you or someone you know is struggling with an eating disorder. Treatment may involve therapy, medication, and nutritional counseling to address the physical and psychological aspects of the condition. With proper care, recovery from an eating disorder is possible.

Polymyositis: An Inflammatory Disorder Causing Muscle Weakness

Polymyositis is an inflammatory disorder that causes symmetrical, proximal muscle weakness. It is believed to be a T-cell mediated cytotoxic process directed against muscle fibers and can be idiopathic or associated with connective tissue disorders. This condition is often associated with malignancy and typically affects middle-aged women more than men.

One variant of the disease is dermatomyositis, which is characterized by prominent skin manifestations such as a purple (heliotrope) rash on the cheeks and eyelids. Other features of polymyositis include Raynaud’s, respiratory muscle weakness, dysphagia, and dysphonia. Interstitial lung disease, such as fibrosing alveolitis or organizing pneumonia, is seen in around 20% of patients and indicates a poor prognosis.

To diagnose polymyositis, doctors may perform various tests, including an elevated creatine kinase, EMG, muscle biopsy, and anti-synthetase antibodies. Anti-Jo-1 antibodies are seen in a pattern of disease associated with lung involvement, Raynaud’s, and fever.

The management of polymyositis involves high-dose corticosteroids tapered as symptoms improve. Azathioprine may also be used as a steroid-sparing agent. Overall, polymyositis is a challenging condition that requires careful management and monitoring.

Neuroleptic Malignant Syndrome

Neuroleptic malignant syndrome (NMS) is a serious medical condition that is commonly caused by potent neuroleptics. Its major features include rigidity, altered mental state, autonomic dysfunction, fever, and high creatinine kinase. The condition can lead to potential complications such as rhabdomyolysis and acute renal failure.

The treatment of choice for NMS is dantrolene and bromocriptine. However, withdrawal of neuroleptic treatment is mandatory to prevent further complications. It is important to note that NMS can be life-threatening and requires immediate medical attention. Therefore, it is crucial to recognize the symptoms and seek medical help as soon as possible.