Systolic murmur is produced in the following conditions
Incompetence of Atrioventricular Valves
When the atrioventricular valves become weak, these valves cannot close completely. This causes regurgitation of blood from ventricles to the atria during ventricular systole producing the murmur. It is a harsh blowing sound with high frequency.
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Maintaining the reading frame during translation is central to the accuracy and fidelity of translation. However, many retroviruses, including HIV, the human immunodeficiency virus that causes AIDS, take advantage of mRNA slippage and a change in reading frame to generate different proteins from the same message.
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In the past, evolutionary studies of species have depended soley on anatomical changes observed in fossil records and on carbon dating. More recently, these studies are being suported by the molecular analysis of the sequence and size of selected genes or whole DNA molecules. Evolutionary altertions of a selected DNA molecule from different species can rapidly be assessed by restriction endonuclease mapping. Generation of restriction endonuclease maps requires a pure preparation of DNA. Mammalian mitochondria contain a covalently closed circular DNA molecule of 16,569 base pair that can rapidly be purified from cells. The mitochondrial DNA can be employed directly for the study of evolutionary changes in DNA without the need of cloning a specific gene.
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Polymerase Chain Reaction and Screening for Human Immunodeficiency Virus
The use of the polymerase chain reaction (PCR) to amplify minute quantities of DNA has revolutionized the ability to detect and analyze DNA species. With PCR it is possible to synthesize sufficient DNA for analysis. Conventional methods for detection and identification of the human immunodeficiency virus (HIV), such as Southern blot-DNA hybridization and antigen analysis, are labor intensive and expensive and have low sensitivity. An infected individual, with no sign of AIDS (acquired immune deficiency syndrome), may test false negative for HIV by these procedures. Early detection of HIV infections in these individuals is crucial to initiate treatment and/or monitor the progression of their disease. In addition, a sensitive method is required to be certain that blood contributed by donors does not contain HIV. PCR amplication of potential HIV DNA sequences within DNA isolated from an individual’s white blood cells permits the identification of viral infections prior to appearance of antibodies, the so-called seronegative state. Current methods are too costly to apply this testing to large-scale screening of donor blood samples. PCR can also be used to increase the sensitivity to detect and characterize DNA sequences of any other human infectious pathogen.
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|This Article is in Category Biochemical techniques
In patients with malignant hyperthermia, a variety of agents, especially, the widely used general anesthetic halothane, will produce a dramatic rise in body temperature, metabolic and respiratory acidosis, hyperkalemia, and muscle rigidity. This genetic abnormality occurs in about 1 in 15,000 children and 1 in 50,000-100,000 older peoples. It is dominantly inherited. Death may result the first time a susceptible person is anesthetized. Onset occurs within minutes of medicine exposure and the hyperthermia must be recognized immediately. Packing the patient in ice is effective and should be accompanied by measures to combat acidosis. The medicine dantrolene is also effective.
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Cytochrome P450 forms play a major role in estrogen synthesis. During pregnancy, a unique interaction among cytochrome P450 forms in different organs is needed in order to synthesize the large quantities that are required. Hormone production increases dramatically during pregnancy and, at term, the pregnant woman produces 15-20mg of estradiol, 50-100 mg of estriol, and approximately 250 mg of progesterone per 24-h period. The amount of estrogen synthesized during pregnancy far exceeds the amount synthesized by nonpregnant women. For example, the pregnant woman at the end of gestation produces 1000 times more estrogen than premenopausal women per day.
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The amount of energy required for any individual varies directly with the degree of activity and environmental conditions, but the rate of energy production in an individual by its over-all cellular metabolism is more or less constant under some standard conditions “basal conditions” and is known as “basal metabolism”.
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In worldwide terms nutritional disorders are responsible for much morbidity and mortality. The three main categories of nutritional disorders are under nutrition (which is dominated by insufficient food energy), producing the features of starvation, malnutrition, which is deficiency, of one or more of the essential nutrients; and obesity, which is excessive positive energy balance. Disease is also possible as a result of nutrient excess
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The incidence of pancreatic carcinoma is increasing tremendously. Increasing evidence suggests that it may result from exposure to chemical carcinogens. Lowest socioeconomic classes and people in urban regions develop more. Individuals of either male or female who smoke one to two packs of cigarette per day have a two to three folds increased risk of developing this cancer.
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In order of increasing frequency, the following are the commonest causes of nipple discharge in the non lactating breast: carcinoma, intraductal papilloma, and mammary dysplasia with ectasia of the ducts. The important characteristics of the discharge and some other factors to be evaluated by history and physical examination are as follows:
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This common benign neoplasm occurs most frequently in young women, usually within 20 years after puberty. It is somewhat more frequent and tends to occur at an earlier age in black than in white women. Multiple tumors in one or both breasts are found in 10-15% of patients.
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Mammary Dysplasia (Fibrocystic Disease)
Essential of Diagnosis
• Painful, often multiple, usually bilateral masses in the breast.
• Rapid fluctuation in the size of the masses is common.
• Frequently, pain occurs or increases and size increases during premenstrual phase of cycle.
• Most common age is 30-50. Rare in post menopausal women. Read complete articles »
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Essentials of diagnosis
• Obstructive jaundice (may be painless).
• Enlarged gallbladder (may be painful).
• Upper abdominal pain with radiation to back, weight loss, and thrombophlebitis are usually late manifestations. Read complete articles »
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Chronic pancreatitis occurs most often in patients with alcoholism, hereditary pancreatitis, severe malnutrition or untreated hyperparathyroidism, or it may be idiopathic. Progressive fibrosis and destruction of functioning glandular tissue occur as a result. Pancreaticolithiasis and obstruction of the duodenal end of the pancreatic duct are often present. (Acute pancreatitis recurring after cholecystectomy for cholelithiasis should raise the suspicion of a retained or newly developed common duct stone.)
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Acute Pancreatitis
Essentials of Diagnosis
• Abrupt onset of deep epigastric pain, often with radiation to the back.
• Nausea, vomiting, sweating, weakness
• Abdominal tenderness and distention, fever.
• Leukocytosis, elevated serum amylase, elevated serum lipase.
• History of previous episodes, often related to alcohol intake.
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I-cell disease (mucolipidosis 2) and pseudo-Hurler polydystrophy (mucolipidosis 3) are related diseases that arise from defects in Lysosomal enzyme targeting because of a deficiency in the enzyme that transfers N-acetyglucosamine phosphate to the high-mannose type oligosaccharides of proteins destined for the lysosome.
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Intravesical chemotherapy
Immuno or chemotherapeutic agents can be delivered directly into the bladder by a urethral catheter. They can be used to eradicate existing disease or to reduce the likelihood of recurrence in those who have undergone complete transurethral resection. Such therapy is more effective in the latter situation. Most agents are administered weekly for 6-12 weeks. The use of maintenance therapy after the initial induction regimen may be beneficial. Efficacy may be increased by prolonging contact time to 2 hours. Common agents include thiotepa, mitomycin, doxorubicin and BCG, the latter being the most effective agent when compared with the others. Side effects of Intravesical chemotherapy include Irritative voiding symptoms and hemorrhagic cystitis. Systemic effects are rare. Patients who develop symptoms from BCG may require antituberculous therapy.
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For the right diagnosis of a particular disease, it is always better to estimate a few (three or more) serum enzymes, instead of a single enzyme. Examples of enzyme patterns in important diseases are given here.
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Primary tumors of the kidney
Renal cell carcinoma
Essentials of diagnosis
• Gross or microscopic hematuria
• Flank pain or mass in some patients.
• Systemic symptoms such as fever, weight loss may be prominent
• Solid renal mass on imaging Read complete articles »
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Although nitric oxide is essential in tumoricidal and bactericidal functions of macrophages, overproduction of nitric oxide has been implicated in septic/cytokine-induced circulatory shock in humans through the activation of guanylate cyclase. This mechanism is responsible for profound hypotension in postoperative patients whose recovery is complicated by bacterial infections that produce endotoxins. Hypotension in these patients is often refractory to treatment with conventional vasoconstrictor medicines. Therapeutic intervention by NOS inhibitors is being examined in inflammatory diseases of the gastrointestinal tract, such as pancreatitis and ulcerative colitis, and in arthritis.
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Essentials of diagnosis
• Irritative voiding symptoms.
• Gross or microscopic hematuria.
• Positive urinary cytology in most patients.
• Filling defect within bladder noted on imaging. Read complete articles »
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Symptoms and signs
Most prostatic cancers are detected in asymptomatic men who are found to have focal nodules or areas of induration within the prostate at the time of digital rectal examination.
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Essentials of diagnosis
• Prostatic indurations on digital rectal examination or elevation of PSA.
• Most often asymptomatic.
• Systemic symptoms (weight loss, bone pain) in 20% of patients. Read complete articles »
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Stress tests, or graded exercise tests, are conducted primarily to aid in diagnosing or quantifying heart or lung disease and to evaluate the functional capacity asymptomatic individuals. The tests are usually given on motorized treadmills or bicycle ergometers (stationary, variable-resistance bicycles). Workload intensity (how hard the subject is working) is adjusted by progressively increasing the speed and the incline of the treadmill or by progressively increasing the pedaling frequency and resistance on the bicycle. The test starts at a low intensity and continues until a prespecified workload is achieved, physiologic symptoms occur, or the subject is too fatigued to continue.
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A group of cells having the same origin, similar shape and specific or common generalized function is known as a tissue. The tissues are classified into four major groups. They are epithelial tissue, connective tissue, muscular tissue, nervous tissue. These four groups of tissues are called elementary tissues.
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Chromatography is one of the most useful and popular tools of biochemistry. It is an analytical technique dealing with the separation of closely related compounds from a mixture. These include proteins, peptides, amino acids, lipids, carbohydrates, vitamins and medicines.
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|This Article is in Category Biochemical techniques
Flow Cytometry has numerous applications and as in case of PCR it might be said that the applications of flow Cytometry are limited only by our own imagination. A detailed discussion of these applications is impossible her. However, major well documented applications have been cursorily dealt with.
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|This Article is in Category Biochemical techniques
Many authorities recommend screening asymptomatic individuals by measuring plasma cholesterol. A level less than 200 mg% is considered desirable, and a level over 240 mg% requires lipoprotein analysis, especially determination of LDL cholesterol. Reduction of LDL cholesterol depends on dietary restriction of cholesterol to less than 300mg day -1, of calories to attain ideal body weight, and of total fat intake to less than 30% of total calories. Approximately two-thirds of the fat should be mono- or polyunsaturated. The second line of therapy is with medicines. Cholestyramine and colestipol are bile salt-binding medicines that promote excretion of bile salts in the stool. This in turn increases the rate of hepatic bile salt synthesis and of LDL uptake by the liver. Lovastatin is an inhibitor of HMG CoA reductase. Since this enzyme is limiting for cholesterol synthesis, lovastatin decreases endogenous synthesis of cholesterol and stimulates uptake of LDL via the receptor. The combination of lovastatin and Cholestyramine is sometimes used for severe hyperlipidemia.
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There is numerous application of PCR and since the techniques is comparatively recent, new applications are being added with an amazing speed. We will not discuss the applications which are common and which can easily be imagined by the reader. Instead some of the novel applications of PCR are discussed in this section.
PCR in cancer research
Since clinical markers of predictive value are not available for cancers, PCR is not yet of much diagnostic value for this human malady. However, PCR is being tremendously used to gain insights into the molecular basis of cancer.
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Traditional laboratory tests for the diagnosis of genetic diseases are mostly based on the estimation of metabolites and/or enzymes. This is usually done after the onset of symptoms.
The laboratory tests based on DNA analysis can specifically diagnose the inherited diseases at the genetic level. DNA-based tests are useful to discover, well in advance, whether the individuals or their offsprings are at risk for any genetic disease. Further, such tests can also be employed for the prenatal diagnosis of hereditary disorders, besides identifying the carriers of genetic diseases.
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Polymerase chain reaction and screening for human immunodeficiency virus
The use of the polymerase chain reaction (PCR) to amplify minute quantities of DNA has revolutionized the ability to detect and analyze DNA species. With PCR it is possible to synthesize sufficient DNA for analysis. Conventional methods for detection and identification of the human immunodeficiency virus (HIV), such as Southern blot-DNA hybridization and antigen analysis, are labor intensive and expensive and have low sensitivity. An infected individual, with no sign of aids, may test false negative for HIV by these procedures. Early detection of HIV infections in these individual is crucial to initiate treatment and/or monitor the progression of their disease. In addition, a sensitive method is required to be certain that blood contributed by donors does not contain HIV. PCR amplification of potential HIV DNA sequences within DNA isolated from an individual’s white blood cells permits the identification of viral infections prior to appearance of antibodies, the so-called seronegative state. Current methods are too costly to apply this testing to large-scale screening of donor blood samples. PCR can also be used to increase the sensitivity to detect and characterize DNA sequences of any other human infectious pathogen.
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|This Article is in Category Biochemical techniques
The use of DNA analysis is a novel and revolutionary approach for specifically identifying the disease-causing pathogenic organisms. This is in contrast to the traditional methods of disease diagnosis by detection of enzymes, antibodies etc., besides the microscopic examination of pathogens. Although at present not in widespread use, DNA analysis may soon take over the traditional diagnostic tests in the years to come. Diagnosis of selected diseases by genetically engineered techniques or DNA probes or direct DNA analysis is briefly described.
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Defects in mismatch repair cause hereditary nonpolyposis colon cancer (HNPCC) and probably are important in other cancers. This was initially suggested by the finding that some colon tumors showed frequent mutations in microsatellites (short repeating sequences, particularly mono- and dinucleotides), a phenotype called microsatellite instability.
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Unexplained weight loss may be a sign of malignancy, and weight loss is common in advanced cancer. Decreased appetite and food intake contribute to but do not entirely account for the weight loss. The weight loss is largely from skeletal muscle and adipose tissue, with relative sparing of c (i.e., liver, kidney, and heart). Although tumors commonly exhibit high rates of glycolysis and release lactate, the energy requirement of the tumor probably does not explain weight loss because weight loss can occur with even small tumors. In addition, the presence of another energy-requiring growth, the fetus in a pregnant woman, does not normally lead to weight loss. Several endocrine abnormalities have been recognized in cancer patients. They tend to be insulin-resistant, have higher cortisol levels, and have a higher basal metabolic rate compared with controls matched for weight loss. Two other phenomena may contribute to the metabolic disturbances.
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Breast carcinoma is moderately sensitive to multiple antitumor agents and combinations of medicines produce higher response rates and longer durations of response and survival than single-agent therapy. Within the past decade a number of new agents have been developed and proved effective in the treatment of breast cancer. The most prominent are the taxanes, including paclitaxel and docetaxel. These taxanes are currently being used in combination with other active medicines including the anthracyclines, cisplatin and its analogs, alkylating agents, antimetabolites, Vinca alkaloids, and anti-estrogens. Recent advances in our understanding of the basic biology of breast carcinoma, including the internal and external stimuli that result in malignant transformation, progression, transformation, and metastasis, have provided additional potential targets for therapeutic intervention.
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Cancer is defined as the excessive division of cells. It is recognized pathologically by a higher fraction of cells actively in the cell cycle than is expected for the normal tissue from which it arose. This includes a higher fraction of cells in mitosis, recognizable by microscopy, and a higher fraction of cells in S-phase.
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Coomassie brilliant blue Staining
This is the most often used protein stain. It is extremely sensitive and becomes even more sensitive in the presence of sodium dodecyl sulphate. It can be carried out by two variants of what is principally one single method.
The first step is to fix the separated proteins. This is achieved by soaking the gels overnight in about 10-12 volumes of 20% sulphasalicyclic acid. This step is followed by staining where the gels are allowed to soak in an aqueous solution of Coomassie blue (0.25%). There is no fixed period for staining. However, higher percentage gels require higher periods of staining. Thus, while 2 hours are sufficient for 5% acrylamide gels, more than 4 hours are required for staining 10% acrylamide gels. Excess stain is removed by washing the gel with successive volumes of 7% acetic acid.
