An infant with a large VSD will fail to thrive and become sweaty and tachypnoeic (breathe faster) with feeds.The restrictive ventricular septal defects (smaller defects) are associated with a louder murmur and more palpable thrill (grade IV murmur). Larger defects may eventually be associated with pulmonary hypertension due to the increased blood flow. Over time this may lead to an Eisenmengers syndrome the original VSD operating with a left-to-right shunt, now becomes a right-to-left shunt because of the increased pressures in the pulmonary vascular bed. Cause
Congenital VSDs are frequently associated with other congenital conditions, such as Down syndrome.A VSD can also form a few days after a myocardial infarction (heart attack) due to mechanical tearing of the septal wall, before scar tissue forms, when macrophages start remodeling the dead heart tissue. A congenital VSD can result from a disturbance in the morphogenesis of the heart in its embryonic stages. In the fifth week of gestation, the heart undergoes multiple processes of septation and forming a dextral loop. Interfering with the latter leads to insufficient leftward movement of the ventricular outflow tract over the atrioventricular canal, which in turn can result in a VSD or, in the most extreme cases, a double outlet right ventricle with one.A ventricular septal defect arises when the superior part of the interventricular septum, which separates the right and left ventricles of the heart, fails to fully develop.
Under ideal program conditions, MDR-TB cure rates can approach 70%. Mechanism of drug resistance
The TB bacterium has natural defenses against some drugs, and can acquire drug resistance through genetic mutations. The bacterium does not have the ability to transfer genes for resistance between organisms through plasmids (see horizontal transfer). Some mechanisms of drug resistance include:
Cell wall: The cell wall of M. tuberculosis (TB) contains complex lipid molecules which act as a barrier to stop drugs from entering the cell. Drug modifying & inactivating enzymes: The TB genome codes for enzymes (proteins) that inactivate drug molecules. These enzymes are usually phosphorylate, acetylate, or adenylate drug compounds. Drug efflux systems: The TB cell contains molecular systems that actively pump drug molecules out of the cell. Mutations: Spontaneous mutations in the TB genome can alter proteins which are the target of drugs, making the bacteria drug-resistant.One example is a mutation in the rpoB gene, which encodes the beta subunit of the bacteriums RNA polymerase. In non-resistant TB, rifampin binds the beta subunit of RNA polymerase and disrupt transcription elongation. Mutation in the rpoB gene changes the sequence of amino acids and eventual conformation of the beta subunit. In this case rifampin can no longer bind or prevent transcription, and the bacterium is resistant.Other mutations make the bacterium resistant to other drugs. For example, there are many mutations that confer resistance to isoniazid (INH), including in the genes katG, inhA, ahpC and others.