Urinary Incontinence

 

                                           Urinary Incontinence

                                             P.K.Ghatak, MD

Urinary incontinence is the medical term for leakage of urine; the common expression is wetting the underpants or simply an accident.

In children, voiding is brought under control several months (between 12 and 30 months) after birth, about the time the baby learns to walk independently. The nerve fibers in certain areas have delayed myelination. Myelin is a fatty substance that gives the nerve fibers a coat of insulation so the nerve impulse from the center/brain can reach the intended organs/ tissues and not be allowed to short out on the way.

The urinary bladder has both involuntary and voluntary muscles. At the apex of the urinary bladder, at the point where the urethra (a tube that carries urine) begins, there is an involuntary muscular sphincter that must relax to permit the urine to flow out of the urinary bladder. Another muscular sphincter, which is made up of voluntary muscles, is present just after it emerges from the pelvic floor and is called the external sphincter. It is under the voluntary control of the Pudendal nerves. It keeps the external sphincter closed until the time to void. It works by withdrawing inhibition and producing contraction of voluntary muscles.

                                             Nerve controlling the urinary bladder.

Three sets of nerves innervate the urinary bladder. Sympathetic, parasympathetic, and somatic nerves. Stimulation of the sympathetic nervous system produces holding of urine; the parasympathetic nerve is the nerve of evacuation of urine. Pudendal nerves are the final arbitrator either to void or to hold urine and are totally under voluntary control.

The lumber segment of the spinal cord supplies the sympathetic fibers to the inferior hypogastric ganglion and the hypogastric nerve carries the impulse to the bladder and internal sphincter. Sacral 1 and sacral 2 segments supply parasympathetic fibers to the parasympathetic ganglion, which supply the postganglionic fibers to the bladder and internal sphincter.

Anterior horn cells of the sacral 1 and sacral 2 segments and lower lumbar nerves form the pelvic plexus from which the Pudendal nerves arise. The two are mixed nerves; they carry both sensory and motor stimulation.

Micturition reflex.

The center for the micturition is situated in the Pons of the brain.

Sensory information is carried from the bladder to the autonomic nerve center in the hypothalamus, which sends impulses to the pons for action. Somatic sensation is carried to the thalamus via the lateral spinothalamic tract, and then to the sensory cerebral cortex. Information for voluntary actions carried from the micturition center via the pudendal nerves to the bladder and the external sphincter.

After voluntary micturition is started, the sensory input continues to flow to the center from the passage of urine through the urethra and the state of the bladder. Voluntary voiding is also helped by the contraction of abdominal muscles. Voiding can be stopped and restarted by volition.

With these pieces of information at the back of the mind, it will be a lot easier to understand why a person develops urinary incontinence.

Urinary incontinence has several independent causes; at times, more than one reason may be present. 

1. Malalignment of the urethra with the bladder.

The urinary bladder rests on a muscular sling made by a group of pelvic muscles. The apex of the bladder continues as the urethra in the same straight line. The bladder is fairly mobile, allowing it to increase and decrease in size as urine is collected continuously and emptied periodically.

Repeated childbirth and loss of muscle mass in menopause, the muscular sling becomes flabby, and the bladder sags downwards. Urethra's alignment is altered and results in voiding difficulties and retention of urine in the bladder. A similar situation arises in men with the hypertrophy of the prostate gland. Other conditions are pelvic tumors, fractures of the pelvic bones, and hematomas. Sneezing, coughing, laughing, and vigorous exercise, etc., produce leakage of urine from a full bladder.

2. Nerve damage.

Sensory nerve damage is often due to diabetes mellitus, both type 2 and type 1. Diabetes can also produce motor nerve damage. In the absence of sensation from an overfilled bladder, the pressure inside the bladder becomes higher than the resistance the internal sphincter can provide and the urine begins to leak. The damage to the peripheral nerve in diabetes starts at the far end of the nerve fibers and progressively approaches the nerve cells. Toes and fingers show the damage first, but the process starts in all the systemic nerve fibers. The autonomic nervous system is generally spared unless the process is very aggressive and of longer duration. Other causes of peripheral neuropathy are - alcoholism, vitamin B1 and B12 deficiency, injury to nerve fibers in an accident or surgery, and hypothyroidism. Several types of infections produce neuropathy - Lyme disease, HIV, and shingles. Other causes of neuropathy generally spare the bladder.

3. Brain and spinal cord vascular events and injury.

The brain instructs the spinal centers for voluntary actions. It also sends inhibitory control over the lower motor neurons situated at the anterior horn cells of the spinal cord. In brain injury, like the middle cerebral artery stroke, that inhibitory control is lost and spasticity of muscles develops due to unopposed reflex contraction of muscles. The urinary bladder becomes small and urine drips continuously. Spinal cord injuries and transverse myelitis are additional conditions producing a similar incontinence. In a few CNS diseases, the urinary incontinence is invariably present, examples - Multiple sclerosis, Parkinson's disease, Alzheimer's disease, Chronic bilateral subdural hematoma and Low pressure hydrocephalus.

4. Muscle diseases.

In inherited muscle diseases, such as Charcot-Marie-Tooth disease, the urinary bladder loses muscle and fails to empty, and incontinence follows. Similarly, in spinomuscular atrophy, the bladder loses muscle control and incontinence.

5. Prolonged bed rest and long term placement of urinary catheters.

The capacity of the urinary bladder is 500ml; however, if a lesser volume is used over some duration, the bladder adopts a lower volume. In prolonged use of an indwelling catheter, the sphincters become incontinent.

In prolonged bed rest, the pelvic muscles become flabby from non-use and the alignment of the urethra is altered and urinary retention and incontinence develop.

6. Repeated or chronic urinary bladder infection.

Infection derails normal control of bladder functions, develops an urge to urinate, frequency, a smaller capacity, and incontinence.

7. Functional or emotional causes.

Psychosis and severe depression produce changes in the perception of normal senses, and the loss of voluntary actions occurs in a timely fashion.

8. Adverse effects of medication.

Hypnotics, sedatives, and anti depression medications have adverse effects on the urinary center and on the bladder and urinary sphincters. In males, Anticholinergic drugs produce dysuria and retention of urine.

8. Pregnancy.

In normal pregnancy, as the gravid uterus enlarges and grows upwards, it raises the bladder neck with it, the bladder capacity also increases, and some retention of urine is normal. In advanced pregnancy, wetting undergarments occurs often.

Incidence of urinary incontinence.

There are about 13 million cases of urinary incontinence in the USA alone. About half of them are nursing home residents. In general, female patients outnumber male patients. Most of the patients are elderly with various chronic illnesses; younger patients are those with developmental delays or have congenital neurological diseases. Spinal cord injury sustained in sports and auto accidents accounts for a handful.

Prevention and Treatment of Urinary Incontinence.

Training at the toilet starts in early childhood. It requires a great deal of patience and love in toilet training. It is important not to threaten or punish a child for an accidental bed-wetting. Fear and intimidation are very counterproductive.

In alcoholism, diabetes mellitus, prompt medical management and timely treatment with antibiotics of infections go a long way to avoid the development of urinary incontinence. Obstruction to the bladder neck by an enlarged prostate gland in males and pelvic tumors in both sexes should be addressed surgically. Prolonged indwelling catheters should be avoided, and various alternative methods to indwelling catheters are available and should be used. Retraining of voluntary voiding should be the goal in all cases where intact bladder innervation is preserved, and that should include CVA and spinal cord injury.

Surgical treatment:

In advanced pelvic malignancy, the bladder may have to be removed. A urinary conduit is created from a loop of the ilium. At times, transcutaneous stents are placed to drain the urine from both ureters. Various other forms of urinary diversion operations are used based on specific circumstances.

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Whipple's disease

 

                                            Whipple's disease

                                           P.K.Ghatak, M.D

Whipple's disease is a bacterial infection of the jejunum, manifest as malabsorption of fat, fat soluble vitamins, and protein.

Dr. George Whipple, in 1907, described the first case in a 36 yr old man who presented with malabsorption associated with lymph nodes enlargement of the mesentery and increased skin pigmentation. He found a small rod-shaped organism in the tissue stained with silver stain, but could not grow it in any artificial media to make a positive identification, and predicted the possibility of a bacterial infection. In 1992, a gram positive coccobacillus was identified in the biopsy tissue by electron microscopy. The bacteria were PAS (periodic acid-Schiff stain) positive and Acid-fast stain negative. The organism is named- Tropheryma whipplei (T. whipplei). T. whipplei belongs to the Actinomycetes group and its pathology has many similarities with Mycobacterium avium intracellulare infection.

The natural habitat of T. whipplei is in the soil, and farmers are three times more likely to develop clinical signs of infection than people in other professions. 51% of the world population are positive for T. whipplei antibodies; however, only 3 in 1 million develop clinical signs of illness. This is due to cellular immune deficiency, which contributes to the development of illness. Farmers who are haplotype for HLA B27 have phagocytes which fail to digest engulfed bacteria because of the lack of activation of CD11 b (integrin alpha) by TH1 lymphocytes.

Mode of infection and incubation period.

The mode of infection and the incubation period are not known precisely, but the oral route is most likely. These bacteria have a three layered outer membrane and which helps them to withstand digestion by the strong Hydrochloric acid (HCl) in the stomach. Once T. whipplei are in the duodenum and the Jejunum, they infect the surface cells of the villi. The cellular infiltration follows, and it produces edema of the villi, and this is the beginning of abdominal symptoms of bloating, cramps and diarrhea. The macrophages engulf the T. whipplei but are unable to kill the bacteria. Macrophages move to lymph follicles in the lamina propria. Nodularity of lymph follicles develops in the lamina propria and also in the mesentery. These two features – edema of villi and enlarged lymph follicles - are characteristics of Whipple's disease.

The second most frequent clinical feature is a reactive type of arthritis of the finger joints and metacarpal phalangeal joints resembling Rheumatoid arthritis, but the Rh factor is negative and erosion of bones does not develop. Similar symptoms also occur in the sacroiliac joints, ankles, and knees,  but less frequently. Other features are anemia, low grade fever, lymph node enlargement, and increased skin pigmentation. Occasionally, cerebellar ataxia, peripheral neuropathy, headaches, oculomotor palsy and seizures may be present. These non-GI symptoms are due to increased production of acute-phase reactants as a result of infection of the GI tract by T. whipplei.

Diagnosis.

Investigation of Malabsorption syndrome includes an upper GI endoscopy with biopsy and the T. whipplei infection can be identified by histopathology, electron microscopy, PAS and acid-fast staining, and also by PCR identification of bacterial DNA.

Treatment:

T. whipplei, not unlike Mycobacterium avium intracellulare, requires prolonged antibacterial therapy followed by a year or two of chemoprophylaxis.

For acute phase infection.

The standard regimen. Ceftriaxone 1 gm IV every 12 hrs., or high dose of Penicillin IV for 2 to 4 weeks. Followed by one to two years of Sulfamethoxazole Trimethoprim 800 mg/160mg tablet twice a day for 1 to 2 years.

Alternate regimen. Doxycycline 200 mg, by mouth daily every 12 hrs., plus Hydroxychloroquine 600 mg orally, once daily for 18 months, followed by Doxycycline 200 mg orally, daily for the lifetime.

For CNS symptoms. Ceftriaxone  2 gm IV every 12 hrs. for 6 weeks, followed by Sulfamethoxazole Trimethoprim twice a day for 1 to 2 years.

Whipple's disease is a bacterial disease due to the immune system's failure in eliminating the pathogenic organism from the body. Articles presented earlier dealt with a virus that remains in hibernation after an infection and subsequently causes a new disease - the Burkitt lymphoma virus. Similarly, a fungus- Pneumocystis jirovecii, and a protozoa, Toxoplasma gondii, were discussed. This article on Whipple's disease concludes this section.

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Stories Nails tell

 

                                                 Stories nails tell.

                                                P.K.Ghatak, MD

Nails are skin appendages. Finger nails are colorless and semitransparent; the blood vessels underneath show through the nail beds of the fingers. Medical practitioners have been observing and deducing the state of health of their patients for centuries. This examination skill is dying out these days, due to the use of technologies which are more precise, but not all of them are readily available at the bedside and they increase the cost of medical care.

Fingernails grow about 3.5 mm a month. It takes 6 months for the nail to reach the tip of the finger. So, nails have many stories to tell about the health condition of an individual over a period of the past 6 months. Some of the physicians who described changes in nails as a result of the underlying diseases have their names attached to those conditions and are still in use today – a few examples are as follows.

Beau's Lines:

 Lines form across the nails seen in Raynaud's disease, injuries to the nails, and chemotherapy and nutritional deficiency. Cold sensitive constriction of the arteries of the hands, producing severe blanching of fingers, followed by severe pain in fingers and blue discoloration of nail beds and tip of fingers, nose, and ears, is known as Raynaud's disease.

Muehrcke's Line:

 In protein deficiency in Nephrotic syndrome, Cirrhosis of the liver, and famine, white lines develop across the nails.

Drier's disease. An autosomal dominant inherited multisystem disorder appears in late childhood and early adolescence, manifests as short stature, greasy confluent skin rashes, generally in the legs, and deformed finger nails with vertical striations.

Color changes indicating underlying diseases:

1. Cyanosis.

Blueish discoloration of nail beds due to hypoxemia can arise from vasoconstriction of vessels of the hands or due to under saturation of arterial blood from diseases of lungs or admixture of venous and arterial blood in the heart chamber due to defects in the partitioning septal walls producing right to left shunt (called Central Cause, in short). In Central Cyanosis, the tongue turns blue. In vasoconstriction, the nail beds are blue, but the tongue remains a normal pink color.

2. Methemoglobinemia.

The RBCs carry oxygen in a loose combination with hemoglobin and the iron molecule in the hemoglobin remains in ferrous form; less than 3 % of oxygen is carried as an oxidized compound – methemoglobin. Here, the iron is oxidized to a ferric form. The ferric iron does not part oxygen to the tissue and the tissue suffers from hypoxia. Abnormally high concentration of oxidized hemoglobin in blood may happen following local anesthesia with benzocaine or tetracaine. The nail beds turn gray. Drugs containing aniline, benzene derivatives and nitrite commonly produce similar changes in hemoglobin; most common among the group are dapsone (used for leprosy), nitrates (used for angina pectoris), and benzocaine (local anesthetic).

Congenital Methemoglobinemia.

Navajo and Athabaskan Indian tribes have higher instances of Cytochrome b5 encoding gene mutations and congenital methemoglobinemia. G6PD (glucose 6-phosphate dehydrogenase deficiency) also produces congenital methemoglobinemia.

Hypoxia in methemoglobinemia is not reversed by Oxygen. Methylene blue and other reducing agents are used therapeutically for that purpose.

3. Carbon monoxide poisoning:

Smokers' blood contains a low level of carbon monoxide (CO). Accidental exposure to CO happens in winter months from indoor coal burning, or keeping a gas cooking range burning through the night for heat. Incomplete burning of coal and natural gas produces CO, and inhaled CO produces high levels of Carboxyhemoglobin in blood. The nails change to a cherry red color. Unless promptly treated, CO poisoning is usually fatal or leaves patients with serious neurological deficiencies,

4. Anemia.

Pale fingernails in anemia is a late sign; the tongue and the conjunctivae of the lower eyelids become pale much earlier.

5. Obstructive jaundice.

When the bile duct is blocked by gallstones or carcinoma of the head of the pancreas, the bile can not drain into the small intestine. The accumulated bilirubin turns the conjunctiva, the skin, and the nails deep yellow.

Other congenital abnormalities of nails.

1. Yellow nail patella syndrome.

Yellow nail patella syndrome is a multisystem structural abnormality of the skeletal system. Dermal and neurological systems. The chromosome 9 carries the genetic mutation that normally encodes a transcription factor for early separation of dermatomes into neuroectoderm, ectoderm, and mesoderm. All three divisions exhibit developmental abnormalities of varying degrees, however, changes in the patella and the nail are constant. It is inherited by an autosomal dominant mode with variable penetrance. The patella is hypoplastic or often absent, the finger nails are deformed or small and yellow in color and brittle; less frequently, the toenails are also deformed. Finger joints and elbow joints are hyperextensible. The iliac bones show horn-like outgrowths and the neck is long like a swan. The separation of neurons into dopamine and serotonin producing lines is defective. The connective tissue formation around the developing eyes and podocytes of the glomerulus of the kidney is defective. Some children develop a condition similar to Duchenne muscular dystrophy.

2. Nonsyndromic congenital deformed nails condition 10.

This is an autosomal recessive inherited disorder of the EZD6 gene, which encodes Frizzled6 protein of the nails. Both fingernails and toenails are extremely thick and hard and easily separate from the nail bed. At times, some toes and fingers are missing.

3. Psoriasis.

Psoriasis is an autoimmune disease of the skin, dead skin cells accumulate under the nail and the nails are pitted.

4. Yellow nail syndrome. 

A rare disease of unknown cause; arises spontaneously and may also resolve spontaneously. It is a combination of slow, hard, thick, and yellow nail, sinus congestion and lower respiratory tract infection, occasionally associated with cylous pleural effusion and lymphedema of hands and feet.

Genome-wide association studies showed 60 susceptible regions of genes involved in Thymic 17 cell actions, which are linked to psoriasis. Linkage analysis identified 9 additional regions - PSORS 1 to PSORS 9. PSORS 2 is inherited in an autosomal dominant mode and it is the common variant in North America. CARD 14 gene, normally encodes an adapter protein of skin keratinocytes and mutation of this gene is linked to psoriasis.

Nearly 80 % of psoriatic patients have one or more changes in the fingernails and also in the toenails. The common presentation is pitted nails. The other changes are white, brown, or yellow discoloration, heaped up dead skin underneath the nail, separating the nail from the nail bed, and brittle nails. Flame-shaped hemorrhagic steaks are occasionally seen.

Fungal infection.

Diabetic patients are more susceptible to fungal infection of toenails and less commonly to fingernails. Dishwashers and other professions in which contact with water is nearly constant are subject to fungal nail infections. Candida species and Trichophyton fungi are common fungal infections of nails.

Common manifestations of fungal nail infections are a change of color to white, black, green, or yellow. Thickening of the nails is also often seen. Nails become brittle and take unusual shapes and textures. Pressure on pain is a common finding. Toenail fungal infection is much more common in diabetics and workers who require wearing boots for long hours.

Systemic illness.

1. Splinter hemorrhages.

Red blood streaks appear under the finger nails due to exudation of blood from the capillaries. These are 1 to 3 mm long, run vertically, and are in multiple nails. Besides bacterial infection of the endothelium, leukemia, use of anticoagulants, certain cancer drugs and nail injuries and lupus erythematosus are also responsible for splinter hemorrhages.

2. Clubbing.

The fingers normally taper from palm to fingertip. Clubbing is an acquired deformity of the tip of the finger, appearing like a drumstick with a bulbous end. Many lung conditions result in chronic low blood oxygen, which produces finger clubbing, chief among them are Bronchiectasis, Non-Small cell cancer of the lung, Mesothelioma, Cystic fibrosis, and lung abscess. Other less often causes are empyema, amyloidosis, idiopathic pulmonary fibrosis and Sarcoidosis. Some non-pulmonary causes are Coarctation of the aorta, aneurysm of the subclavian artery, A-V fistula, Congenital heart diseases, Crohn's disease and ulcerative colitis, cirrhosis of the liver, malabsorption syndrome, and Graves' disease of the thyroid gland.

Other less frequent nail changes.

1. Hollowed out nail beds resembling spoons are seen in malnutrition.

2. A dark gray to black streak along the length should raise suspicion of melanoma.

3. Some people have habits of pushing back the cuticles of their nails repeatedly, producing multiple ridges and grooves in the center of nail beds. It is called Onchotillomania.

4. Half white and half pink nails are common in chronic renal failure patients.

5. In cirrhosis of the liver, nails turn white. White spots on nails are present in Zinc and iron deficiency

6. People engaged in silver mining develop blueish nails. In a congenital Copper metabolic disease, Wilson's disease blue mails may be present due to deposition of copper in the tissues.

7. In vitamin B12 deficiency anemia, nails may turn black in color. In an injury to the nails, blood under the nail beds appears black. The normal half moon of nail beds may be absent in chronic lung and heart diseases.

8. Use of hair coloring shampoo usually stains fingernails of various colors, but the colors are just stains and can be easily removed by nail polish remover.

Paronychia.

Paronychia is an infection of the soft tissues on the sides of the nail. When the cuticle of the finer nail is damaged, bacteria and fungi grow, and an abscess may develop. Paronychia is painful and requires local treatment with antibiotic ointment and, rarely, incision and drainage of an abscess. Streptococcus pyogenes and Staphylococcus aureus are common bacteria - if the infection source is from water, the organism is Pseudomonas bacteria, and the pus is green in color.  Of the fungi, Candida species is common.

edited June 2026.

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Heart Failure

 

                                                  Heart failure

                                                P. K. Ghatak, M.D.

The human heart is divided into 4 chambers. The two upper chambers receive blood and the two lower chambers - the right and left ventricles- discharge blood and are muscular in nature and are called muscular pumps. The right ventricle sends venous blood to the lungs for collecting fresh Oxygen and discharge Carbon dioxide. The distance between the right ventricle and lungs is short, and the right ventricle has to generate just enough pressure to send blood into the pulmonary capillaries.

The left ventricle is responsible for sending fully oxygenated blood and nutrients to every cell of the body and requires to generate much higher pressure and has a thick muscular wall.

The failure of one or both ventricles to send blood out to their respective destinations happens when ventricular muscles become weaker. This is medically termed as heart failure; it may occur only on the right side, in which case it is called right ventricular failure, and similarly, when only the left ventricle fails, it is called left ventricular failure. Often, one ventricular failure progresses to both heart failures and also both hearts may fail simultaneously. If heart failure happens suddenly, it is called acute heart failure – either acute right heart failure or acute left heart failure. And when heart failure develops over the years, it is called Chronic Heart Failure – chronic right heart failure or chronic left heart failure, or simple heart failure. Heart failure or ventricular failure is the same, and one term is used for the other quite frequently.

The cause of heart failure:

Blood is the vital fluid; the circulation of blood to every cell of the body is the only function of the heart. Blood loss due to accident or surgery and chronic anemia are known causes of heart failure, but are not discussed here.

Causes of Heart Failure:

The heart fails due to various medical conditions and the conditions are either congenital or acquired.

1. Abnormal Coronary Artery:

The ventricles of the heart are full of blood but unable to use that blood for their oxygen and nutritional requirements. Coronary arteries supply blood to the heart. Coronary artery disease is the most common reason the heart fails to supply blood to the heart. It may happen suddenly – known as an acute coronary event and unless immediate hospital treatment is received, a devastating result follows; the heart may fail slowly over the years – in this situation, angina pectoris (pain in the heart) is the main symptom. Then the heart muscles slowly weaken and fail.

High BP, high cholesterol, obesity, genetic predisposition, and diabetes are risk factors for the development of coronary artery disease. Initially, the endothelial cell damage separates cells and serum sips underneath the endothelial lining. A waxy deposit forms, pushing it inside the lumen of the vessel, blood flow slows and that manifests as angina pectoris. From time to time, the waxy plaque breaks and sends the tissue debris further into a smaller arteriole and precipitates a heart attack. In the raw area of the wall - the site of plaque break, platelets accumulate to plug the raw area by forming a platelet clot, followed by a blood clot that develops and blocks off the coronary artery. 

2. Diabetes mellitus.

This condition is steadily increasing all over the world as more and more people are consuming factory-produced prepackaged food. Diabetes produces microvascular changes in the coronary vessels and many other organs. Plaque formation in the coronary artery leads to heart attacks as described above.

{wish to know how DM produces microvascular changes....https://humihealth.blogspot.com/2022/01/diabetes-mellitus-and-microvascular.html}

High BP causes the ventricular muscles to undergo hypertrophy in order to overcome the resistance offered by high BP. Coronary arteries pass through the layers of the heart muscle and every time the ventricles contract, the coronary artery is pinched off. Higher BP means more pinching and less and less blood flow to the ventricles. If high BP is not controlled, the heart muscles weaken and fail.

These three conditions are the main causes of heart failure.

   4. Pulmonary embolism.

Deep seated veins of the thigh and pelvis, under certain conditions, spontaneously develop blood clots. Venous clots are fragile and easily break off and are carried by the venous blood to the right side of the heart. The right ventricle pushes these clots into the pulmonary artery, and the clots block pulmonary arterial circulation. Patients experience severe chest pain, palpitations and begin to sweat and soon go into shock. Blood returning to the left ventricle from the lungs is markedly undersaturated and patients develop central cyanosis. Symptoms of hypoxemia are soon followed by cardiac arrhythmias and shock, which do not reverse with beta-adrenergic drugs and other measures. Death follows hours or in a day or two.

The above 4 are also examples of output failure of the ventricles.

5. Cardiac tamponade and pericardial effusion.

When the pericardial cavity is filled with blood because of a direct injury or due to rupture of the heart from other causes, there is little space remaining in the ventricles to receive blood. This condition produces stagnation of blood in the pulmonary circulation and is followed by the systemic circulation. Cardiac arrhythmia and shock soon follow.

6. Constrictive pericarditis.

Certain infective pericarditis ends in thickening of the pericardium and sometimes develops calcification. The symptoms produced in this condition are not that dramatic, but nevertheless serious enough to threaten the life of a patient if prompt treatment is not forthcoming.

7. Myocarditis and dilated cardiomyopathy.

Viruses commonly associated with myocarditis are Adenovirus, Parvovirus B19, Human Herpes virus 6, Epstein-Barr virus, Human Cytomegalovirus, and Enterovirus. Initial inflammatory cell infiltration of the myocardium is followed by fibrosis. The ventricular muscles become weak and unable to meet the body's demand, and the heart fails. In this condition, dilated cardiomyopathy and atrial fibrillation and ventricular fibrillation may end life earlier than heart failure.

8. Subacute bacterial endocarditis.

Streptococcus viridans infects damaged or deformed heart valves – the mitral and aortic valves are mostly bacterial growth. This produces further damage to valves and other vulnerable ventricular structures and systemic sepsis leads to organ failure and death.

Staphylococcus and many other bacteria and fungi are capable of causing myocarditis and more easily damage heart structures.

9. Infiltrative diseases of the heart.

Like inflammatory cells, other substances like iron, copper, and amyloid, a proteinaceous material, infiltrate ventricular muscles. This interferes with ventricular functions and eventually the heart fails.

10. Radiation and chemotherapy.

Doxorubicin and other chemotherapy drugs and radiation therapy are cardiotoxic and ultimately produce cardiac fibrosis and heart failure.

Examples 5 to 10 are also considered diastolic dysfunction of the ventricles (defect in receiving blood).

Other less common but significant causes of heart failure.

1. Morbid obesity and Kyphoscoliosis.

The way the heart functions normally requires free movements inside the chest cavity, as it beats. These two examples and several conditions put strain on the heart, and the right ventricle fails first.

2. Malignancy.

Tumors of the heart are rare. Rarely, sarcoma of the heart is encountered. It is not an easy task to care for.

3. Congenital defects of the heart.

The advent of Doppler Sonography makes it possible to examine a developing child in utero and if there are structural defects of the heart, that can be surgically repaired at that time or shortly after birth. This has eliminated many instances of heart failure. Just to mention some well known congenital heart lesions are Atrial Septal Defect (ASD), Ventricular Septal Defect (VSD), Pulmonary Stenosis (PS), Fallot Tetralogy and Transposition of Great Vessels. Hypertrophic cardiomyopathy is congenital, but symptoms start at age 16 -18. In the congenital anomalous origin of a coronary artery arising from the coronary sinus, venous blood circulates through the myocardium. In postpartum, the baby fails to thrive and dies if the condition is not recognized soon enough. 

4. Acquired heart valve defects.

Rheumatic fever, at an earlier time, produced havoc with the lives of many young individuals. The streptococcus sore throat is the initial illness, followed by 2 weeks later by joint pain and heart murmurs, the Mitral valve is always affected and often associated with the Aortic valve

5. Atrial fibrillation and ventricular fibrillation.

These two heart rhythm abnormalities are seen less frequently in otherwise younger, healthy individuals and are considered as diseases of the old. However, cocaine, amphetamine and cannabis users are distinct health hazards. When ventricles pump 250 -300 beats per minute, this is hardly enough time for blood to enter the ventricles and cardiac output falls precipitously. It does not take much for patients to lose consciousness and, without treatment die from shock. In ventricular fibrillation, the heart does not actually contract, and blood remains in the cavities of the ventricles, and blood circulation ceases.

 The New York Heart Association classified heart failure into 4 categories based on the severity of the symptoms. In category 1 - patients have minimal symptoms, in category IV - patients are bedridden and totally dependent on others for the activities of daily living. Categories II and III are in between Categories II and III.

This list of causes of heart failure is short; conditions that are not primarily cardiac are not included in this article.

This blog may be better understood if a previous blog, Human Heart, is also reviewed at the same time.

https://humihealth.blogspot.com/2019/03/the-heart-and-heart-failure.html   (Copy and paste on your browser).

revised July 2025

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Toxoplasma gondii

                                                  Toxoplasma gondii infection

                                                               P.K. Ghatak, MD 

Toxoplasma gondii

Toxoplasma gondii is a protozoan. It lives in cats' intestine as a parasite and is eliminated from cats' body in the feces in a cystic form, from which it can infect mammals and birds. Rodents and small mammals are intermediate hosts, and humans are also intermediate hosts and victims.

Toxoplasma needs a higher concentration of arachidonic acid, a long chain fatty acid, for sexual maturity and reproduction. All species of cat family provide that environment because the enzyme, delta-6-desaturase (D6D), which breaks down arachidonic acid during metabolism, is lacking in the cats' small intestine.

Toxoplasmosis is a medical term describing clinical features of Toxoplasma gondii (T. gondii) infection. T. gondii is an obligate intracellular parasite in humans and other mammals.

Eating undercooked meat, raw fruits, vegetables,  and drinking unfiltered water contaminated with cat feces are the main sources of human infection. In rare cases, blood transfusion, organ transplantation and transplacental infection to the developing fetus can occur. Most infected people show no symptoms, however, the fetuses of women infected for the first time during pregnancy and Immunosuppressed people become sick.

There are three infectious forms of T. gondii, - 1. sporozoites - present in the feces of cat as oocysts (thick wall cysts containing multiple larvae), 2. tachyzoites (rapidly multiplying by asexual cell division) and 3. bradyzoites (slow growing or dormant) - present in the muscles and organs of infected mammals.

Life cycle of Toxoplasma.

T. gondii has a complex life cycle.

In cats:

All species of the cat family are carnivorous, when they devour infected prey, the cysts are released in the small intestine. The wall of the cysts opens and releases sporozoites. Subsequent development of T. gondii takes two different pathways.

1. As an intestinal parasite.

In 3 to 10 days, the sporozoites mature as male and female gametes and after mating, they begin to reproduce. Millions of cysts are excreted daily in the feces for 14 days. In the soil, these cysts mature further and become infectious in a day or two. The cysts can survive about a year in the soil and water

2. As cysts in muscles and organs,

Some of the released sporozoites penetrate the intestinal wall and are carried by the blood to different organs and muscles. The sporozoites asexually divide rapidly and are called tachyzoites. Later, tachyzoites stop dividing and form cysts and are known as bradyzoites. Cysts in the muscles, heart, eyes and other organs can complete their life journey if other carnivores eat the cat.

In rodents, mammals and humans:

Infection is via the oral route. In the intestine, the T. gondii follows the 2nd path described for cats.

                                         Taken from CDC publication.

Primary infection occurs in healthy adults.

About 50% of infected people have no symptoms, the rest have symptoms resembling a flu with slight fever, body aches, cough and sneezing. Cervical lymph node enlargement is a distinct feature, at times, lymph nodes draining the thorax may enlarge. Viral pneumonia like symptoms may develop in some. Rarely, skin lesions of various definitions are also described. Cysts, containing a live T. gondii, remain in the muscles, brain, heart, eyes and other organs for the rest of the life of an individual.

Pregnancy:

In the first trimester of pregnancy, if a woman is infected, there is a good chance that infection from the placenta will pass to the fetus. This may result in a miscarriage and spontaneous abortion. A growing fetus examined by ultrasonography shows growth retardation and a characteristic triad of hydrocephalus, chorioretinitis and areas of calcification of the brain. Eye infection leads to congenital blindness. And sensory deafness in 30% of cases.

In the last trimester of infection, it produces mainly blindness.

Latency:

In all healthy people, T. gondii after the initial infection, remains in an inactive state. The organism, however, is still alive within the cysts and lasts for the rest of the life of the individual.

Reactivation:

When inter-current infections and HIV infection in particular, lower the cellular resistance or immunosuppressed drugs are used, the cellular resistance breaks down and T. gondii spread throughout the body. The CNS and eye symptoms predominate.

The Brain:

Mass lesions, like cerebral lymphoma, are present in many cases; in most of the cases,  necrotizing lymphocytic vasculitis and microglial nodules around the cysts are present. These produce seizures and symptoms of encephalitis. The common areas of the brain are the symmetrical lesions in the white matter of the cerebral cortex, the thalamus, the brain stem, and the cerebellum. Symptoms are headaches, confusion, a seizure, inability to concentrate, clumsiness of movements, fever and nausea and vomiting.

Eyes:

Necrotizing lesions of choroid and retina of the eyes produce poor vision and blindness.

Diagnosis:

The initial test is IgM and IgG antibodies against T. gondii. If a biopsy is performed, the T. gondii is visible within the cells. In most cases, a PCR test to detect DNA of T. gondii has become a standard test. In encephalitis, the PCR test of CSF is 100% positive.

In suspected mother to fetal transmission, an amniocentesis and PCR test is performed on the amniotic fluid.

Treatment:

Normal adult people with T. gondii infection require no medication. In a developing fetus, even if infection is confirmed, no anti-protozoal drugs are prescribed because of adverse effects. After the birth of the baby, the choice of therapy is a combination of Pyrimethamine and Sulfadiazine. Infections of pregnant women, if the child is not infected, - Spiramycin is the preferred therapy. If the child is infected, then no treatment is given to mothers in the first trimester because drugs can cause deformed brain development and low platelet count of the child. After 16 weeks of pregnancy, Pyrimethamine and Sulfadiazine plus folinic acid are prescribed.

In all other infections, the drug of choice is a combination of Pyrimethamine and Sulfadiazine; Folinic acid is added to prevent anemia.

Children with congenital deafness, 16 months of therapy is advocated.

Prophylaxis in HIV infection and immunosuppressed individuals.

Pyrimethamine plus Sulfadiazine should be continued.

Vaccine:

No vaccine is available.

Prevention:

Good hygienic measures and avoiding undercooked meat and unwashed fruits and vegetables.

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Burkitt Lymphoma Virus

 

                                                   Burkitt-Lymphoma Virus 

                                             Now known as Epstein-Barr Virus

                                                     P.K.Ghatak, MD.

Epstein-Barr Virus (EBV) was originally known as Burkitt Lymphoma Virus.   Dr. Denis P. Burkitt (from Ireland), a surgeon working in Uganda, reported a highly aggressive Head and Neck lymphoma of children in 1958. He sent biopsy specimens to Dr. Epstein, a Pathologist in the UK. Dr. Epstein, a virologist from Ireland and Dr. Achlonga, a Pathologist with an interest in electron microscopy originally from Trinidad, worked together and identified a virus in the biopsy tissue. They reported their finding in 1964 and named the virus, Burkitt lymphoma virus. This is the first virus identified as the cause of human malignancy – the first human oncogene. The virus is known today as Epstein-Barr virus - EBV in short.

This article on EBV is the 3rd and last of a series of viruses after producing the primary illness, then enter a latent period. In certain circumstances, the virus is reactivated and produces different illnesses. The EBV infects B-lymphocytes and B-memory cells and remains dormant in these cells. EBV is known to produce several malignancies and other medical illnesses when it reactivates.

In a previous blog, many aspects of the EBV were discussed, this article is a supplement to - 

https://humihealth.blogspot.com/search?q=Epstein+Barr+virus.

EBV infects children and young adults worldwide. Saliva of the infected people contains EBV and kissing is the common mode of spread of EBV. Contaminated utensils, food and drinks are additional modes of spread. Blood transfusion, organ transplants and sexual activity also spread EBV.

Infectious Mononucleosis is the primary illness.

Incubation period is long, 4 to 6 weeks. The symptoms are that of a URI, but distinctive features of EB virus infection are enlarged and edematous tonsils. Posterior cervical lymph node enlargement in addition to enlarged circular and longitudinal chains of cervical nodes and occasionally intrathoracic and axillary lymph nodes enlargement. The spleen is enlarged and may rupture with minor trauma. Liver enlargement is also seen

Another distinguishing feature is salmon colored morbilliform eruptions on the trunk in about 10% of cases; those who do not have skin lesions will develop itchy but similar skin eruptions if they receive Ampicillin. Peripheral blood examination shows lymphocytosis and large atypical lymphocytes - resembling monocytes, and that was the basis of calling the illness as Infectious mononucleosis. IgM antibody appears early and persists for 6 weeks, the IgG antibody appears later and remains positive for the life of the patient.

Latent period:

The latency is divided into 3 stages.

In the 1^st stage of latency, the virus remains totally inactive, except in Burkitt lymphoma. The initial adenopathy progresses to lymphoma in a short time.

In the 2^nd stage, the virus is only partly active and interferes with nucleic acid synthesis of the host cells, this results in gene mutation and subsequently chromosome breakage and fusion of genes.

In the final 3^rd stage, the EBV is fully active and produces several malignancies and illnesses as listed below.

Illness produced after the virus is reactivated:

A. Malignancy-

Evidence points directly to EBV.

1. Burkitt lymphoma.

2. Undifferentiated Nasopharyngeal carcinoma.

3. Hodgkin lymphoma and perhaps non-Hodgkin lymphoma.

4. Lymphomas - designate as 1. Diffuse Large. 2. B-cell. 3. Extranodal T/NK. 4. Plasmablastic.5. Primary diffuse.

5. Hairy cell leukemia.

Evidence of EBV is strong but the question remains -

1. Epithelial cell cancer of the stomach.

2. Epithelial cells cancers of Tonsils, Thymus, Breasts, Skin, Uterine cervix,

3. Lymphoepithelial cancer of salivary glands.

Questionable association with EBV -

1. Renal cell cancer

2. Thyroid gland

3. Urinary bladder.

4. Leiomyoma / Leiomyosarcoma.

B. Non-Malignant Diseases.

Autoimmune diseases like 1. Sjögren's syndrome 2. Rheumatoid arthritis. 3. SLE, 4. Type 1 Diabetes mellitus. 5. Hashimoto thyroiditis. 6. Graves' disease. 7. Multiple Sclerosis. 8. Hairy Leukoplakia.

Chronic illness.

    1. Long COVID-19

2. Chronic Mononucleosis. Symptoms are fatigue, fever, lymph node enlargement, Hepatosplenomegaly, headaches, joint pain and muscle pain.

3. Parkinson's disease and Acute cerebellar ataxia.

4. Irritable Bowel syndrome.

5. Chronic fatigue syndrome.

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Chickenpox

                                               Chickenpox (varicella)

                                                P.K. Ghatak, MD.

Varicella virus causes Chickenpox when a person contacts the virus for the first time. After recovery, the virus remains dormant in the nerve cells of the cranial nerve ganglia, the dorsal root ganglia of the spinal cord and the autonomic ganglia, for the entire life of the individual. In an opportune moment, the virus re-emerges and produces Zoster (Shingles) and occasionally produces more serious neurological complications. The virus called Varicella Zoster Virus (VZV)

VZV is an alpha herpesvirus. It is human herpesvirus 3 and has almost identical genomes of the Simian Pox virus (SPV). Some of the pathophysiological features of VZV are similar to Cytomegalovirus.

VZV has a double-stranded DNA genome, surrounded by a nucleocapsid followed by a protein integument and a lipid envelope.

The initial infection activates cellular immune reactions followed by IgM, IgG, and IgA antibodies production. Cellular immunity provides lifelong protection.

In the USA, a vaccine is routinely administered as a part of childhood vaccination, the vaccine is made from attenuated live VZV. Adults over 50 years of age are urged to take a second approved Zoster vaccine. This is a non-live recombinant zoster vaccine. It is given by intramuscular injection – two doses 2 to 6 months apart. It reduces the risk of herpes zoster by 92 %. The vaccine is named Shringrix and it protects vaccinated people for up to 9 years.

Clinical features of Chickenpox.

Chickenpox infection is a common infection of childhood. It is a highly communicable disease. It is estimated that over 90 % of the world population had chickenpox. The mode of infection is by droplets and also the virus becomes airborne from a raw wound of an open vesicle. The incubation period in 10 to 15 days may be delayed to 3 weeks. The initial symptoms are cold and cough, fever, and body aches, followed by erythematous skin rashes, followed by papular eruptions, which appear the next day. The papular lesions appear first on the chest, back and then on the face, followed by outward spread to the arms and legs but no lesions appear on the palms and soles. In 2 to 3 days, vesicles become embellicted and crusted. Mixed rashes consisting of papules, vesicles and crusted lesions are present at any time, which is a distinguishing feature of chickenpox from smallpox. The skin rashes are intensely itchy. In about one week, the scabs begin to fall off. From the day of onset of respiratory symptoms to crusting, all vesicles of the patient remain infectious.

Vulnerable populations are pregnant women who did not have chickenpox before. HIV infection, cancer chemotherapy, long term steroid therapy, and organ transplant patients.

Complications:

Young adult male and adult males in some instances develop orchitis, epididymitis and testicular atrophy. In a few cases, pancreatitis is reported. In rare cases, viral pneumonia can occur.

Neurological complication from Chickenpox.

The common neurological complication is cerebellitis (infection of the cerebellum). In rare cases, central vein thrombosis and strokes are recorded.

Since childhood vaccination was introduced in the USA, hardly any new cases of chickenpox are seen. Immune status is judged by serology. It is a mandatory test for all prenatal care in the USA.

Diagnosis and Treatment:

Clinical features are distinct and since most older adults had chickenpox, that helps them in diagnosis. In doubtful cases, viral DNA, a specimen obtained from a vesicle, by PCR may be required.

The choice of antivirus drug is Acyclovir. The oral dose is 800 mg, given 5 times a day for 5 days, (200mg/Kg/day). Other antivirals used in Cytomegalovirus infection are also effective in chickenpox.

Varicella-Zoster Immune Globulin (VZIG):

VZIG is given as IM injection, never by IV. The therapy is a passive transfer of immunity in life-threatening situations.

Indication of VZIG.

Premature infants of immune-negative mothers. Pregnant women past 1 week of gestation with unvaccinated or negative history of previous VZV infection (seronegative). Bone marrow transplants in seronegative patients. Immune compromised patients.  Passive immunity is followed by vaccination. 

Reactivation of VZV.

Immunosuppressive conditions lead to the reactivation of VZV.  Nerve cells of all cranial nerve ganglia, Autonomic ganglion and sensory Dorsal Root Ganglion of spinal nerves are at risk of resurgence and Zoster lesions. The virus produces vasculopathy with loss of cells and focal migration of inflammatory cells and giant cell formation. This causes pain, paresthesia and loss of motor function of the dermatome the nerves supply. The pain is sharp and severe and localized to the dermatome involved and strictly limited to one side of the body. The motor fibers of the spinal cord are commonly affected, producing palsy (partial paralysis). The vesicles appear as bunches, like grapes, are strictly limited to the side of the body and do not cross the midline. Multiple dermatomes and contiguous dermatome and multiple dermatomes of different areas of the body may be involved. In some instances, no skin lesions develop, only pain is experienced.

The common places herpes zoster appears are the chest wall, followed by the face. Of the cranial nerves, the 5^th cranial nerve is most common. It produces pain and vesicular lesions of one half of the face, eyelids, and forehead.

In rare circumstances, the virus travels to the brain and meninges via the sensory nerve from the Geniculate ganglion (ganglion of the 5th cranial nerve) producing meningoencephalitis.

Ramsay Haunt Syndrome:

Ramsay-Hunt syndrome is a special case of herpes zoster involving multiple cranial nerves. The ganglia of the 7^th,8^th, 9^th, and 10^th nerves are involved. This causes severe pain, vesicular eruptions on dermatomes and mouth, tongue, and throat of the area supplied by the nerves. Skin lesions appear on the external ear canal, pinna (supplied by 10^th), one half of the anterior 2/3rd of the tongue and soft palate and uvula. 7^th cranial nerve lesions produce lower motor neuron paralysis and the stapedius muscle. 8^th cranial nerve lesion produces loss of hearing, tinnitus, nausea, vomiting, vertigo and nystagmus. 9^th and 10^th cranial nerve lesions result in paralysis of the tongue, muscles of deglutition. Chorda tympani nerve lesion causes loss of taste sensation.

Diagnosis and treatment:

Clinical features are diagnostic and confirmation if required, the PCR test for viral antigen is available. The choice of antiviral agent is Acyclovir. Other antiviral agents used in chickenpox are also effective in Zoster lesions.. In addition to viral therapy, prevention of secondary bacterial infection of the skin and mouth lesions and adequate management of pain by opioid derivatives by mouth should be provided.

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Cytomegalovirus

 

                                                             Cytomegalovirus;

                                                             P.K. Ghatak, MD.

                                                        Cytomegalovirus.

Cytomegalovirus belongs to the Beta Herpesvirus group. Cytomegalovirus is species specific. Herpesvirus 5 is a Human Herpesvirus. Genome specific virulence is characteristic of this virus. It prefers to grow in human fibrocytes and produces a large inclusion body. This gave this virus its name as " large cell” Cytomegalovirus 5 (CMV). Once inside the human body, it produces primary infection and after the infection subsides, CMV hibernates in lymphocytes, monocytes, dendritic cells and CD34+ cells and remains dormant for the entire life of the person.

The virus is large, has a diameter of 200 nanometers and the nucleus contains double stranded DNA and the virus is shaped like a disk. CMV has a large genome with an icosahedral capsid and a dense core surrounded by an amorphous matrix.

Humans are infected in several ways –

 1.  During close contacts with an infected person.

2.  From saliva and ingestion of contaminated food and drinks.

3. Via blood transfusion, bone marrow and solid organ transplantation.

 4. Sexual contact.

 5. Placental transmission to fetus.

6. Through breast milk.

The percentage of the population infected with CMV varies from 100% in underdeveloped countries to 40 to 60 % in advanced nations.

The incubation is 8 days to 8 weeks, the majority of infections, in both healthy children and adults, produce minor cold symptoms or no symptoms at all. The only evidence of infection is the séropositive.

In Immunodeficient patients:

The infection is widespread in immunodeficient patients and people on immunosuppressed drugs. CMV infects any organ of the body and in the majority of cases, most organs are infected and the outcome is generally bad. Cell mediated immunity is the primary defense against CMV infection. HIV infection and other clinical conditions where CD4+ and CD8+ cell counts are low, the widespread infection is common. Even after a successful antiviral therapy, the recurrence of infection and chronic infection are common.

CMV remains dormant within the cells and reemerges following other viral infection or other illnesses. This characteristic is similar to varicella virus, Epstein Barr virus and Toxoplasma gondii (a protozoa).

Clinical picture:

The young symptomatic patients present with fever, pharyngitis, cervical adenopathy, and upper and lower respiratory infection. A morbilliform skin rash is generally present, however, skin rashes of various other kinds are also seen. Blood tests may show atypical lymphocytes but the heterophile antibody test is negative (modified Paul Bunuel Test)

In more serious infections, hemolytic anemia and thrombocytopenia are present. Gastritis and colitis may develop. When GI and urinary systems are infected, a prolonged viral shedding is a common occurrence. Meningoencephalitis, myelitis, retinitis, uveitis, and neuropathy are some of the serious aspects of nervous system infection.

The CMV infection is difficult to differentiate on clinical grounds from Infections Mononucleosis. In CMV, the fever generally lasts longer and lymph node enlargements are less extensive.

The definitive diagnosis is by detecting DNA of CMV by the PCR method. Blood, urine, and saliva are suitable for PCR tests but a blood test gives the most conclusive evidence of CMV infection. In post-transplant patients, tissue biopsy is the preferred test.

Important clinical situation of CMV infection.

A. Congenital CMV (cCMV) infection.

B. Stem cell transplantation in hematological malignancy and solid organ transplantation.

 Congenital CMV infection (cCMV).

If a previously uninfected pregnant woman acquires CMV infection in the first trimester, the virus infects the placenta and then infects the developing embryo. Two areas of infections are most critical.

1. Brain development abnormalities and related symptoms 

2. Sensory deafness and blindness.

 Congenital CMV brain and clinical features (cCMV)

Microcephaly, seizure disorder, cerebral atrophy, cystic lesions in the temporal lobes, periventricular calcification and dilated cerebral ventricles, and demyelination. Delayed fetal growth is common.

These changes clinically resemble Cerebral palsy, Multiple sclerosis, Peripheral neuropathies, Leukoencephalomyelitis, and Aicardi-Goutières syndrome (a rare congenital gene mutations resulting in deformed brain and skin lesions).

2. The cCMV is the leading viral, non-genetic, cause of congenital sensory deafness.

Congenital eye infection is a leading cause of childhood vision problems and blindness. Chorioretinitis, uveitis, ophthalmitis and optic atrophy are manifestations of CVM infection. Blindness is due to optic atrophy and detached retina from fibrosis as chorioretinitis heals.

B. Stem Cell Transplants and Solid Organ Transplants, and their relation to CMV.

General consideration.

The CMV status of the recipients is determined by the presence of IgM and IgG antibodies. In allogeneic hemopoietic stem cell transplants, the donor CMV antibody status and immunohistopathology examination of tissue are collected. After the transplantation, if recurrence of CMV is suspected, several additional tests are performed. Presence of Leukocyte CMV pp65 antigen indicates infection and QNAT (quantitative nucleic acid test) is done to determine the viral load.

In both stem cell and solid organ transplants, if the recipient is seropositive, but the donor is seronegative, then the outcome of the transplant is the best. The worst outcome in a situation where the recipient is seronegative and the donor is seropositive. CMV virus reactivates because the use of immunosuppressive drugs depresses T-cell count. Immunosuppression is needed to prevent transplant rejection. The graft versus host disease is another cause of reactivation of CMV. Loss of life occurs in overwhelming CMV infection.

T-cell and Hemopoietic transplant.

During the pre-transplant phase, a high dose of immunosuppressive drugs is used to wipe out all malignant cells from the body. The T-cell count falls to the lowest levels. This is the prime reason for the subsequent reinfection.

Prophylaxis against CMV infection.

The choice of drug is Valganciclovir. It is an oral prodrug of Ganciclovir. Ganciclovir is converted to triphosphate form and inhibits DNA replication of CMV. It can produce cytopenia.

Acyclovir is also used. It is given 800 mg 4 times a day for 12 weeks. Nephrotoxicity and cytopenia are the main side effects.

Other drugs:

a. Letrovir. It inhibits viral terminase enzyme and thereby viral replication. Leterovir can be used more than 100 days without any additional side effects.

b. Foscarnet. It is a phosphate analog of ganciclovir. It inhibits the polymerase enzyme. Furthermore, it is less toxic to bone marrow.

c. Mribavir. It is a benzimidazole antiviral drug. It prevents viral UL97 enzyme. It inhibits viral polymerase.

d. Cidofovir. It is anucleotide analong inhibits polymerase enzyme, given IV weekly.

e. Brincidofovir. It is an oral analog of Cidofovir.

Adoptive T-cell therapy.

Harvested T cells, matched for HLA, are incubated with specific CMV antigen protein. The engineered T-cells are made to multiply in large numbers and then transfused. This is a newer method to control infection in CMV resistant to all drugs.

Vaccine:

A vaccine – Transvax contains a viral plasmid that encodes pp65 and gB glycoprotein, is in use in a pilot study. Two other vaccines, CyMectin and AVX601, contain a viral DNA subunit and use a vector to deliver it.

Treatment of CMV infection/recurrence.

Drug of choice for treatment of CMV viral infection and recurrence is Ganciclovir. Ganciclovir is given 5 mg/Kg/ every 12 hrs. for 14 to 21 days.

Acyclovir is effective but the response in individual patients varies. It is given IV 500 mg per square meter of body surface every 8 hrs. for 2 weeks. A small amount of TNF given with Acyclovir greatly increases the therapeutic effects of acyclovir.

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