Hodgkin's disease AIIMS MCQ for Medical PG preparations

AIIMS MCQ :

The combination of meclorethamine,vincristine, prednisolone, and procarbazine is used for the treatment of patients with:

A. Acute lymphocytic leukemia

B. Chronic lymphocytic leukemia

C. Hodgkin's disease

D. Acute myelocytic leukemia

Ans. C.

·MOPP, the combination regimen of meclorethamine, vincristine (Oncovin), prednisone, and procarbazine, is often alternated with the ABVD regimen [doxorubicin (Adriamycin), bleomycin, vincristine, and dacarbazine in the treatment of patients with Hodgkin's disease, These regimens are based on the use of drugs with different mechanisms of action and different toxicities, so that the cancer cells are attacked at different sites of action, and the collective toxicity is not directed toward one organ system. Mechlorethamine is a nitrogen mustard alkylating agent, vincristine is a mitotic spindle poison, prednisone is a glucocorticoid with lymphotoxic effects, and procarbazinehas multiple actions directed against nucleic acids and proteins. Vincristine and prednisone produce less bone marrow suppression than alkylating agents and antimetabolites.

 

                                     LEPROSY

Definition: Chronic granulomatous infectious disease of skin & peripheral nerves, Caused by Mycobacterium Leprae, also known as Hansen’s disease. Skin, muscles, eyes, bones, testes and internal organs can also be involved.
Etiopathogenesis Causative organism Mycobacterium Leprae is a weak acid fast obligate intracellular bacilli. Discovered by Gerhard Heunk Armauer Hansen in 1873 in Norway.
Can be grown in foot pad of mice & nine banded Armadillos.
Very low infectivity even Conjugal partners have 5% risk of transmission of disease.

genetic susceptibility is also seen
Risk of children acquiring infection from infected adults in the family is 60%.

• Transmission: Still uncertain but most likely, spread s via droplet mode, from untreated patients nasal  mucosa, other routes can be skin to skin or may be via GIT.
• Generation time is 12 days, Incubation period is 2—7 yrs. (average 3-5 yrs)
• The optimal temperature for growth for leprae bacilli is 30 - 33 centigrade
• Virulence factor of M. Leprae is phenolic glycolipid I, a surface lipid, specific to this bacillus.
• Common sites which are involved — Skin, Peripheral Nerve, generally involves every organ except CNS & Ovaries and lungs.
• M. Leprae attacks Schwann cells of peripheral nerves, unmyelinated are more affected.
• Tuberculoid leprosy is the one end of spectrum of disease, is seen in high resistance person
• Lepromatous leprosy is the other end of spectrum of disease, seen in low resistance person.
• Transplacental Infection does not occur
• In India, tuberculoid leprosy is more common as compared to Lepromatous Leprosy.

Some general facts about leprosy ace:
• Cell mediated immune response of the host determine the type of leprosy.
• TT and LL patients are stable
• TT leprosy often self heals, most common type of leprosy in India.
• First clinical symptom in leprosy is numbness. .
• LL leprosy remains heavily infected unless given appropriate chemotherapy.
• BR leprosy is the most unstable, with most patients down grading if not treated
• Leprosy can affect all ages and both sexes.
• The limited growth of M. leprae in the mouse foot pad provided a way to screen for therapeutic agents and to identify drug resistance in leprosy.
• The recognition of leprosy in the nine banded armadillo provided a source of large quantities of highly
 purified M leprae for biochemical anti immunologic studies including preparation of vaccine for leprosy

PRENATAL DIAGNOSTIC TESTING PROCEDURES

Ultrasound

This noninvasive imaging modality is used for guidance of invasive prenatal diagnostic procedures. No adverse effects have been identified when using low-energy transducers. Current recommendations are to perform sonography in pregnancy only for obstetric indications. Optimal gestational age for identification of fetal anatomic structural anomalies is 18—20 weeks. Accuracy of gestational dating is ±5 days at less than 12 weeks, and ±7 days between 12 and 18 weeks. Specificity and sensitivity for identification of fetal anomalies is less than perfect.

Chorionic Villous Sampling (CVS)

This refers to aspiration of placental tissue precursors under sonographic guidance for fetal karyotyping. It is performed between 9 and 12 weeks gestation. Follow-up testing with triple marker screening and sonogram is needed to assess for neural tube defects. Placental mosaicism may be rarely present although fetal karyotype is normal. Pregnancy loss rate is 0.7%. Advantages include the early gestational age at which karyotype is available.

Amniocentesis

This refers to trans-abdominal needle withdrawal of amniotic fluid under sonographic guidance. When performed for genetic purposes (fetal karyotyping, alpha-fetoprotein determination, biochemical studies), the gestational age is usually 15—20 weeks. When performed for Rh isoimmunization (bilirubin level), the gestational age is usually after 24 weeks. When performed for fetal maturity studies (lecithin-sphingomyelin ratio, phosphatidyl glycerol, the gestational age is after 34 weeks. Pregnancy loss rate is 0.5%.

Percutaneous Umbilical Blood Sampling (PUBS)

This refers to sonographically guided transabdominal aspiration of fetal blood from the umbilical vein. It is performed after 20 weeks for fetal karyotyping, IgM antibody detection, blood typing, and intrauterine blood transfusion. Pregnancy loss rate is 1-2%.

Fetoscopy

This largely experimental procedure refers to sonographically guided transabdominal placement of a fiberoptic scope for purposes of fetal tissue biopsy and coagulation of placental vessels in twin- twin transfusion syndrome. It is performed between 18 and 20 weeks in suspected congenital ichthyosis. Pregnancy loss rate is 3—5%. 

Function of the Skin

Function	Structure
Protection from harmful agents of external environment: biological germs, ultraviolet light & chemicals	Epidermis
Preservation of a balanced internal environment	Epidermis
Shock absorber	Subcutaneous fat
Temperature regulation	Blood vessels & eccrine sweat glands
Insulation	Subcutaneous fat
Sensation	Nerve endings
Lubrication	Sebaceous glands
Protection & grip	Nails
Calorie reserve	Subcutaneous fat
Vitamin D synthesis	Epidermis
Body odour	Apocrine sweat glands
Psychosocial	Hair & Nails

                 RHESUS ISOIMMUNIZATION

Rh blood group incompatibility arises when an Rh-negative woman conceives an Rh-positive fetus. RBCs from the fetus can enter the woman’s circulation during pregnancy or, more commonly, during birth. These “foreign” RBCs stimulate the production of maternal anti-bodies against the Rh factor. Spontaneous or induced abortions of an Rh-positive fetus can also result in isoimmunization. In subsequent pregnancies, transplacental transmission of the maternal anti-Rh antibody leads to hemolytic anemia in the fetus or neonate. The resulting disease, called erythroblastosis fetalis, may be fatal. Unless a woman was previously sensitized by transfusion, a first pregnancy rarely leads to erythroblastosis fetalis. Isoimmunization does not have signs or symptoms during pregnancy, although hydrops fetalis and fetal demise may occur in severe cases. In less severe cases, bilirubin levels in the newborncan increase dramatically because of the hemolytic anemia. This can lead to kernicterus, characterized by decreased tone, poor feeding, apnea, seizures, and death. Survivors of kernicterus can be left with mental retardation, choreoathetosis, and hearing loss.

High maternal anti-Rh antibody titers, checked in Rh-negative women at the first prenatal visit and at week 26, suggest sensitization of the mother. Amniocentesis showing high bilirubin levels in theamniotic fluid suggests more severe disease and potential for fetal death.

If bilirubin levels are elevated, intrauterine transfusions to the fetus can be performed at 2-week intervals. Delivery should be minimally traumatic, and the placenta should not be manually removed.

Inthe neonate, hyperbilirubinemia may necessitate phototherapy or an exchange transfusion.
At the first prenatal checkup, all patients should be screened for Rh type. If the patient is Rhnegative, maternal Rh antibody titers should be checked early in the pregnancy and repeated at the twenty-sixth week of gestation. A previously unsensitized mother will not normally produce anti-Rh antibody until after delivery, when mixing of the maternal and fetal blood occurs. Rh isoimmunization can be prevented by injecting the mother with anti-Rh immunoglobulin (RhoGAM) at 28 weeks and within 3 days of delivery. Immunoglobulin C binds the fetal Rh factor and prevents the mother from developing anti-Rh antibodies but is too large to pass though the placenta to the Rh-positive fetus. RhoGAM should be given at the termination of each pregnancy, whether a delivery, ectopic pregnancy, or abortion, as well as any other time when feto-maternal hemorrhage may occur (e.g., amniocentesis or trauma). 

 EPIDERMOLYSIS BULLOSA

 Clinical Features

1 This is extremely rare group of hereditary blistering disorders which are characterized by blisters and erosions resulting from trivial trauma.

2.  Blisters occur soon after birth and mainly concentrate on bony prominence of 4 limbs.

3. An acquired form mimicking Bullous Pemphigoid known as epidermolysis bullosa acquisita (EBA) occurs in adults.

4. Bullae tend to occur at sites of trauma.

5. The IgG in these patients binds to the anchoring fibrils attached to the Lamina densa.

 6. EBA may be associated with underlying systemic diseases like SLE, inflammatory bowel disease, amyloidosis and internal malignancy.

 Investigations

The diagnosis can be confirmed by skin biopsy for histopathology and electronmicroscopy. EBA can be differentiated from bullous pemphigoid by the sodium chloride split skin test and immunofluorescence on the skin specimen. In EBA, the blister occurs below the split, whereas, the blister occurs on the roof of the split in bullous pemphigoid.

Treatment

For the hereditary EB, no effective treatment is available at present. Antenatal diagnosis and genetic counselling can be offered. Systemic steroid can be useful in EBA. 

SOME COMMON ABNORMALITIES IN PERIPHERAL BLOOD SMEAR EXAMINATION

Anisocytosis
Variation in the size of RBC seen in Fe deficiency anemia, megaloblastic anemia, and sideroblastic anemia Poikilocytosis
Variation in the shape of RBC, seen in Fe deficiency anemia, thalassemia, and sideroblastic anemia.
Microcytosis
RBC size less than normal (< 75 fL), seen in Fe deficiency anemia, thalassemia, and sideroblastic anemia

Macrocytosis
size of RBC> 100 fL seen in vitamin B₁₂ and also folic acid deficiency

Hypochromia
RBC with less Hb, the increased central pallor is seen in Iron deficiency anemia, thalassemia, sideroblastic anemia
Basophilic stippling or punctate basophilia

Presence of scattered deep blue dots in the cytoplasm of RBC with Romanowsky staining, seen in pathologically damaged young red cells, severe anemia β thalassemia, and chronic lead poisoning.

Target cells—Flat red cells with a central mass of Hb (dense area) surrounded by a ring of pallor (pale area) and an outer ring of Hb (dense area), seen in chronic liver diseases, hyposplenism, and hemoglobinopathies.

Howell-Jolly bodies—seen in non-functioning or absent spleen and megaloblastic anemia.

Heinz’s bodies (Ehrlich’s bodies)—formed from denatured, aggregated hemoglobin, seen in thalassemia, hemolytic anemia due to G6PD deficiency, asplenia, and chronic liver disase.

Burn cells—RBC showing regularly placed spicules, seen in uremia.

Schistocytes—they are fragmented RBCs seen in intravascular bemolysis.

Spherocytes—small, densely packed RBCs with loss of central pallor, seen in hereditary spherocytosis and immunohemolytic anemias. 

                             VARIOUS DEFORMITIES

• Flexion, adduction, internal rotation: Posterior dislocation of hip.

• Flexion, abduction, external rotation: Anterior dislocation of hip.

• Gun stock deformity, S-shaped deformity, Cubitus varus: Supracondylar (SC) fracture of humerus.

• Dinner fork deformity: Colle’s fracture.

• Simian hand deformity (Ape thumb deformity): Median nerve injury.

• Policeman’s tip hand deformity—ERB ‘S palsy— Proximal (C5-C6 roots) brachial plexus injury.

• Boutonniere deformity (buttonhole deformity): Rheumatoid arthritis (RA) [flexion at proximal mterphalangeal (PIP), hyperextention at distal interphalangeal (DIP) joint].

• Swan neck deformity: RA (hyperextention at PIP, flexion at DIP).

• Intrinsic plus deformity: RA, VIP, cerebral palsy (CP) (flexion at metatarsophalangeal (MP) joints extention at IP joints).

• Intrinsic minus deformity: Leprosy (paralysis of intrinsic muscles).

• Thumb-in-palm deformity: Polio, CP, and stroke.

• Trigger thumb: Congenital constriction of flexorpollicis longus tendon sheath at MP joint.

• Madelung deformity: Wrist deformity (distal and radial bowing of distal radius, shortening of radius, subluxation of inferior radioulnar joint

Note: Distal fragment is the reference point to suggest the type of displacement.

Vegetations
Rheumatic fever	Nonbacterial thrombotic	Libman-Sacks endocarditis (SLE)	Infective endocarditis (IE)
Small ,warty	Small ,single, or multiple	Medium sized (small)	Large
Firm	Friable (Produce emboli)	Single or multiple	Bulky
Multiple	Along lines of closure	Flat, verrucous	Irregular
Friable (but less than those of NBTE)		Irregular	On upper surface of cusps
Along lines of closure of valves		On surface of cusps, both surfaces may be  involved; most common being the undersurface , less often on  mural ebdocardium	Less often on mural endocardium
		In pockets of valves
Sterile (no organisms)	Sterile	Sterile	Nonsterile (bacterial)
No destruction of underlying  valves or myocardium	Nondestructive	Destructive, may damage valve or myocardium	Ulcerates of perforates the underlying valve (or myocardium)
Seen in rheumatic fever	Seen in hypercoagulable states, eg, cancer, Promyelocytic leukemia, increased estrogenic state	Seen in SLE	Seen in IE

USG Obs & Gyne
-Gestational sac is earliest recognized at	5 weeks (32 days by transvaginal sonography)
-Foetal node is earliest recognized at	6 weeks.
-Foetal heart motion is earliest recognized at	6-7 weeks
-Foetal movements are earliest recognised at	8-9 weeks
-Placental implantation is earliest recognized at	8-9 weeks
-Fetal breathing movements are earliest recognized at	11 weeks
-Fetal spine can be recognized earliest at	12 weeks
-Fetal stomach. Kidneys. UB & Cardiac anatomy can   be earliest recognized at	16 weeks
-Fetal genitalia are earliest recognized at	14 weeks
-Epiphysis of distal end of femur can be earliest recognized at	32 weeks

GENETICS

on average, any two individuals share 99.9% of their DNA sequences. Thus, the remarkable diversity of humans is encoded in about 0.1% of our DNA.

FIRST DISEASE IN WHICH GENE THERAPY IS USED--- SEVERE COMBINED IMMUNODEFICIENCY DISEASE (SCID).

Autosomal monosomies are incompatible with fetal development.

Only monosomy compatible with live birth is due to involvement of sex chromatin- turner syndrome(45X)

 Disease with multifactorial inheritance-

Coronary heart disease, diabetes mellitus, cleft lip/cleft palate, hypertension, gout, pyloric stenosis, congenital heart disease.

Prader willi syndrome- paternal genomic imprinting and maternal uniparental disomy (both allele of gene comes from same parent either mother or father).

Autosomal dominant disorder with phenotypically normal parents have more than one affected child-  germline mosaicism.

Karyotyping is not done with the blood monocyte.

Karyotyping with light microscopy is done by- G banding(Giemsa banding)

DNA fragmentation in apoptosis is detected with the help of-  TUNEL( Terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate insitu nick end labelling).

Inheritance pattern of blood group system – by CODOMINANCE

Gene regulating normal morphogenesis during developmentis- Homeobox gene

Most common type of genetic polymorphism- single nucleotide polymorphism(SNP)

Study of multiple genes- Microarray

Blotting techniques-

southern blot- for DNA

Northern blot- for RNA

Western blot- for protein

Chromosomal abnormalities in down syndrome-

Trisomy 21(95%)- maternal non disjunction most common cause

Mosaicism(2%)

Robertsonian translocation(3%)- transfer of genetic material between two metacentric chromosomes.

Lawrence moon biedel syndrome- mental retardation, retinitis pigmentosa, polydactyly, hypogonadotropic hypogonadism, obesity( not asthenic)

Mc cune Albright syndrome- polyostotic form of fibrous dysplasia, pigmentation, precosious puberty(3p), mutation in GNAS α.

Most common cause of ambiguous genitalia in females- complete or classic 21α hydroxylase deficiency.

Rokitansky kuster hauser syndrome- vaginal atresia, absent uterus.

SOME COMMON ABNORMALITIES IN PERIPHERAL BLOOD SMEAR EXAMINATION

Anisocytosis
Variation in the size of RBC seen in Fe deficiency anemia, megaloblastic anemia, and sideroblastic anemia Poikilocytosis
Variation in the shape of RBC, seen in Fe deficiency anemia, thalassemia, and sideroblastic anemia.
Microcytosis
RBC size less than normal (< 75 fL), seen in Fe deficiency anemia, thalassemia, and sideroblastic anemia

Macrocytosis
size of RBC> 100 fL seen in vitamin B₁₂ and also folic acid deficiency

Hypochromia
RBC with less Hb, the increased central pallor is seen in Iron deficiency anemia, thalassemia, sideroblastic anemia
Basophilic stippling or punctate basophilia

Presence of scattered deep blue dots in the cytoplasm of RBC with Romanowsky staining, seen in pathologically damaged young red cells, severe anemia β thalassemia, and chronic lead poisoning.

Target cells—Flat red cells with a central mass of Hb (dense area) surrounded by a ring of pallor (pale area) and an outer ring of Hb (dense area), seen in chronic liver diseases, hyposplenism, and hemoglobinopathies.

Howell-Jolly bodies—seen in non-functioning or absent spleen and megaloblastic anemia.

Heinz’s bodies (Ehrlich’s bodies)—formed from denatured, aggregated hemoglobin, seen in thalassemia, hemolytic anemia due to G6PD deficiency, asplenia, and chronic liver disase.

Burn cells—RBC showing regularly placed spicules, seen in uremia.

Schistocytes—they are fragmented RBCs seen in intravascular bemolysis.

Spherocytes—small, densely packed RBCs with loss of central pallor, seen in hereditary spherocytosis and immunohemolytic anemias

Professional Negligence	Infamous Conduct
Absence of care, skill, willful negligence	Violation of Medical code of Ethics
Damage to person is present	Need not be present
Civil, criminal (trial) courts	State medical Council
Fine, Imprisonment	Erasure of Name
Appeal to higher court	Warning by State / Central govt.

1. The following statement is wrong regarding case control study
A it is useful for rare disease
B Early to do the study
C Incidence can be calculated
D It is a retrospective study 

Ans. C Incidence can be ...
> We cannot measure incidence, and can only estimate the relative risk.
Case control studies, often called ‘retrospective studies’ are a common first approach to test casual hypothesis.
 Case - control study or retrospective study has 3 features:
>Both exposure and out come have occurred before the start of study.
>The study proceeds backwards from effect to cause, (so called retrospective study)
> It uses a control group to come to inference.
> Matching of cases and controls to eliminate confounding factors is done in this study.
>Relative risk & odds ratio can be calculated but not incidence.