Dear medical students & friends,

Hi, I am Dr. Nitin Chawla, Assistant Professor in department of Pathology in SGRR medical college, dehradun. As you all know that based on new MCI curriculum, it is mandatory to ask 20% of questions in university exams in
MCQs format. At times students find it
difficult where to get chapter wise MCQs to assess the study of the topic.
Keeping this in mind, I have written an explanatory MCQ book in pathology “REVIEW OF PATHOLOGY” which contains
MCQs based absolutely from the syllabus prescribed by Medical council of India.
This book caters to medical students based on the syllabus of topics
taught in pathology during second professional. The book offers detailed
chapter wise questions which help students to have thorough insight in the
subject. It is different from other PG medical
entrance guides as it gives chapter wise MCQs from the syllabus and gives
explanation for every answer, whereas other guides offer MCQs mixed up from
entire subject. So, if you really crave to score more marks in second MBBS
university examinations, you can visit the website of the book which is as
follows:

www.reviewofpathology.com

and book your copy.

Note-Kindly tell all your MBBS friends about it.

RECENT ADVANCES IN TREATMENT OF HIV/AIDS PATIENTS
-----DR.D.R.NAKIPURIA
AIDS is acquired immunodeficiency syndrome comprises of many symptoms and signs (different complains of patients and many thing evaluated by Doctor on examination)of Patient suffering from HIV,Hunam Immunedeficiency Virus.AS THE NAME SUGGEST OUR DEFENCE SYSTEM or Immune system is paralysed or made less responsive(measured in this infection by determining CD4 Count from Blood examination as a type of Lymphocyte fighting with invasion of HIV in our Body) whenever any infection of Bacteria,Virus,Fungus or parasite invade our body as a result infection can occur in any part of our body and as primary resistance from our Body System is weak,infection spreads more and more resulting in further growth of invading microbes and this HIV virus too(measured by Viral Load as Copies of Virus in Blood and susceptibility to drugs by sensitivity test).Therefore development of Anti Retro Virus (as HIV is Retrovirus) medicines has developed which once started raise immune system CD4 count by checking further growth of HIV virus and prevent infection by other Microbes(Oppurtinistic Infections) but as we know more and more about these medicines and their side effects and different Oppurtinistic Infections,WHO put some best guidelines when to start these medicines in HIV patients as in Year 2006 ART was to be started if CD4 count is below or 200 but in 2010 it is upto 350 But Amercan Journal suggest it upto 500 when patient is symptomatic or in stage I and II as per WHO staging(Patients with less grade of infections)but in stageIII and Stage IV patients or patients with severe form of disease or seriously ill as suffering from TB,Meningitis,Kidney or Cardiomyopathy,Chest or GI tract infections does not require any estimation of CD4 count as this is presumed and fact that their CD4 count is below 350 or 200 and ART or Better called HAART Medicines immediately.In case of TB patients ATT should be started after start of ART generally within 2-8 wks to avoid IRIS or any adverse reaction,those on HAART developing TB ,ART should be started immediately(with efavirenz except children below 03 yrs of age and first trimester pregnancy).In case of Pregnant Patient same module is practised ,in patients suffering with Hepatitis B or C patients,like TB, ART should be started immediately without any staging or delay of 2-8 wks.In case of Childrens too now same strategy is applied but here CD4 count varies according to age groups,we can start ART immediately in stage III and IV in infant or children upto 12 yrs of age but in Infants and children up to 2yrs of age no need of checking CD4 count start ART if patient is sytomatic or is diagnosed as HIV patients,even in infants now ART may be started if we strongly clinically suspect HIV (As Mother strongly positive or both parents positive or breast fed positive mother children etc) but in early age from 2-5 yrs reduction of CD4 count up to 750 or % of CD4 count below 25 but above 05 yrs criteria is 350 for stage I and II . In Developed countries Art is being started CD4 count upto 500 or less above 05 yrs and adult.CD4 count was previously estimated every 06 months but now at every 03 months and if it is not raising considered as immunological failure and Viral load to be done before starting therapy and also at 3-6 months to see copies below 5000/ml it is raising then drug sensitivity test is done and if not possible then IInd Line drug is started,if IInd line drug started then now a days IIIrd line drug is started.In pregnancy either mother exposed to AER earlier or not ART started in first trimester(avoiding Efavirez) with drug regime and is continued life long unlike nevirapine during labor or Zidovudine regime only,Zidovudine and Nevirapine found good in CD4 count between 250-350.
Now HAART medicines has been slightly modified,Two NRTIs and one NNRTIs is still practised to check drug resistance by Virus mutation but instead of dT4(Stavudine 30 or 40 as per wt above or below 60kg causing severe lididolysis or peripheral neuropathy,pancreatitis ) now3TC(Lamivudine)+AZT/ZDV(Zadivudine causing severe anaemia or neutropenia ) or 3TC + TDF(Tedofil,causing nephropathy and calcinosis ) or TDF + FTC (Emcritabine),AZT+ FTC(causing hepatitis) so 3TC+ AZT+NVP(causing hepatitis and stevenson Zhonson syndrome) or 3TC+AZT+EFV (Efavirenz)or 3TC+TDF+NVP(Nevirapine) or EFV is preferred ,even Simple FTC+NVP or FTC+ EFV is preferred.here Abacavir (ABC) or Diadanosine (ddi) is also used as NRTIS but combination like Stavudine+Zaduvidine,3TC+FTC or AZT+TDF or dt4+Abacavir is not used . Incase of Tuberculosis patients,Efavirenz is given not NVP except when patient is child below 03 yrs or Ist trimester pregnant or under Psychotic condition or medicines.If possible and patient can afford Rifabutine may be started in ATT instead of Rifampcin but mostly if patient is not renal compromised or under hepatic pathology simple ATT is good.In Resistant cases(increase in viral load,less cd4 count or drug resistance)IInd line drug of 03 drugs combination is started here one protease inhibitor(Liponavir(LPV) / Squanavir(SQR)/ Indinavir(IDV) /Atazanavir(ATV) /Fosamprenavir(FPV) / Darunavir(DRV) /Etarvine(ETV) with boosted Ritonavir(r)or plain Ritonavir(RTV) is used and along with this in TB patients with Rifampcin dose of protease inhibitor like Lopinavir+ boosted ritonavir(LPV/r) or Squanavir +Boosted Ritonavir or Indinavir + boosted Ritonavir is increased but with Rifabutine no dose adjustment is done.Instead of using NRTIS used in past as for dt4 or 3TC ,AZT + TDF or TDF + FTC or simply replacing 3TC by TDF or FTC or ABC or ddi is done,if any drug produce complication or side effect as mentioned above it is also replaced.In case of Hepatitis B TDF +3TC is used with NNRTIS or Protease Inhibitor.Revebrine and Pregylated Interferon is used with ART in Hepatits C patients.If after IInd line treatment CD4 count is increased third line treatment using one NNRTIS ,one Protease inhibitor as newly added ATV,DRVor FPV with Integrase inhibitor Raltegravir(RAL) is used.
Cotrimoxazole is added to prophylaxis below 350 to prevent malaria,bacterial,PNeumocystis Jivorecii or Campylobacter Diarrhoea and Toxoplasmosis.STD clinic for any sexual inflicted persons like commercial or flying sex worker (counselling and promoting use of condom )and treatment and screening of suspected highly prone patients like IDUs,drug users,(not sharing needle)migratory labours,Truck drivers etc., at target Intervention clinic is backbone to control it and every suspect should be submitted for HIV screening ,Similiarly every TB patient and in ICTC every Blood donor and PTCT pregnant mother is screened for HIV.Proper counselling of these patients with advise and regular follow up of these persons at primary or semi primary or assisting ART centre is must by doing off and on viral load and CD4 count examination. Every oppurtunistic infection should be controlled and here medicines shold be contined for a long time to prevent recurrence and continuation of ART medicine of great importance.Adhrence,compliance and continued taking medicines with proper counselling during IRIS or any other drug reaction is most important of HIV treatment.

09434143550
Author is an HIV specialist Doctor

Prostate cancer remains the most commonly diagnosed and the third leading cause of cancer deaths among men in western countries , but most men with the disease dont die from it. In the United States a man has 15.8% chance of being diagnosed with prostate cancer but the risk of dying is 2.8%. The American cancer society still recommends that men at high risk and those 50 and over should be screened. Prostate specific antigen (PSA) is a protein produced by the cells of prostate gland. The PSA test measures the level of PSA in blood. Because this antigen is produced by the body and can be used to detect diseases, they are also called biological markers or tumor markers.New studies show that men who have low prostate specific antigen at 60yrs of age , do not really need future screening. But what do you say to men who are 40, 50 or 55 ? All men should start having their PSA levels checked before the age of 60, then at 60 if the PSA is less than 1 nanogram / ml , they are at low risk of prostate cancer. According to researchers , PSA level at age 60 is a good predictor of who were at risk , and that low levels at age 60 means you are unlikely to benefit from subsequent PSA tests as your risk of metastasis or death from prostate cancer is very low.Conversely , men with high PSA reading- 2ng/ ml or above should be monitored and screened, as they are at higher risk. A digital rectal examination (DRE) and PSA levels are used for screening. PSA can be elevated in both benign and cancerous conditions of the prostate , and the level tends to increase with age. The use of age specific PSA reference ranges are suggested as more accurate. Men at risk and above 50 and over should talk with their doctors about the risk and benefits of screening.The American Cancer Society also stresses that in some cases - such as men over 50 who are not expected to live for another 10 yrs , such tests should not be offered because they will cause more harm than good with treatments that has unpleasant side effects such as incontinence and impotence which can greatly affect the quality of their lives.

MULJIBHAI PATEL UROLOGICAL HOSPITAL, NADIAD


JAYARAMDAS PATEL ACADEMIC CENTRE

Retrograde Intra Renal Surgery

Jayaramdas Patel Academic Centre (JPAC) at the Muljibhai Patel Urological Hospital (MPUH), Nadiad is organizing a two-day programme on ‘Retrograde Intra Renal Surgery (RIRS)’ on 16th & 17th September, 2010. Who will be in the driving seat? PCNL, RIRS, ESWL?

RIRS is a procedure for doing surgery within the kidney using a viewing tube called a fiberoptic endoscope. The scope is placed through the urethra (the urinary opening) into the bladder and then through the ureter into the urine-collecting part of the kidney. The scope thus is moved retrograde (up the urinary tract system) to a position within the kidney (intrarenal).

RIRS may be done to remove a stone. The stone is seen through the scope and can then be manipulated or crushed by a pneumatic probe or evaporated by a laser probe or grabbed by small forceps, etc.

The advantages of RIRS over open surgery are that it is a minimally invasive surgery with the elimination of prolonged pain after surgery, and much faster recovery.

Muljibhai Patel Urological Hospital has handled more than 23000 stone cases so far.

The two-day programme will cover all aspects of RIRS. The participants will also be able to see LIVE surgeries of Flexible URS for Lower Calyceal Stone, Calyceal Diverticular Stone, Ectopic Kidney and Mini/Micro perc for Kidney Stone and Ectopic kidney stone.

Faculty from abroad and India will be participating. They include Drs Olivier Traxer (France), M Prabhakar, Pawan Gupta, Anil Bradoo, PP Rao, and Abhay Khandekar. Medical Director and Managing Trustee of MPUH, Dr. Mahesh Desai; and Chairman of Dept of Urology, Dr. R B Sabnis will also be participating in the programme.

P A JOSEPH



P A JOSEPH

Osteogenesis imperfecta
OI and sometimes known as Brittle Bone Disease, or ‘Lobstein syndrome’.Osteogenesis imperfecta is disorder of congenital bone fragility caused by mutations in the genes that codify for type I procollagen. It is a common heritable disorder of collagen synthesis that results in weak bones that are easily fractured and are often deformed. It is also known as Brittle Bone Disease, or ‘Lobstein syndrome’. This condition affects an estimated 6 to 7 per 100,000 people worldwide. Several distinct subtypes have been identified. All of them lead to micromelic (short-limbed) dwarfism of varying degree. Depending on severity, the bone fragility may lead to perinatal death or cause severe deformities that persist into adulthood. A wide array of clinical manifestations of the disease may be seen. These partly depend on the genetic subtype. Types I and IV are the most common forms of osteogenesis imperfecta, affecting 4 to 5 per 100,000 people.

The following 4 types of osteogenesis imperfecta have been reported. Type I - mild forms, type II - extremely severe, type III, severe type IV – undefined.

People with this disease are born with defective connective tissue, or without the ability to make it, usually because of a deficiency of Type-I collagen. This deficiency arises from an amino acid substitution of glycine to bulkier amino acids in the collagen triple helix structure. The larger amino acid side-chains create steric hindrance that creates a "bulge" in the collagen complex. As a result, the body may respond by hydrolyzing the improper collagen structure. If the body does not destroy the improper collagen, the relationship between the collagen fibrils and hydroxyapatite crystals to form bone is altered, causing brittleness. Another suggested disease mechanism is that the stress state within collagen fibrils is altered at the locations of mutations. These recent works suggest that osteogenesis imperfecta must be understood as a multi-scale phenomenon, which involves mechanisms at the genetic, nano-, micro- and macro-level of tissues.
In osteogenesis imperfecta, the modes of inheritance, family history, clinical features, and radiologic findings vary.Four distinct types are identified: type I, which is the dominantly inherited form with blue sclerae; type II, which is the perinatal lethal form; type III, which is the progressively deforming form with normal sclerae; and type IV, which is the dominantly inherited form with normal sclerae.
In general, type I is the mildest form of disease; type IV, type III, and type II, respectively, increase in severity.



As a genetic disorder, Ti is an autosomal dominant defect. Most people with OI receive it from a parent but it can be an individual (de novo or "sporadic") mutation. Osteogenesis imperfecta is relatively rare. In some cases, the parent has osteogenesis imperfecta and the condition has been genetically transmitted to the child. But, the child's symptoms and the degree of disability could be very different from that of the parent. In some children, neither parent has osteogenesis imperfecta. In these cases, the genetic defect is a spontaneous mutation.
The primary pathology in osteogenesis imperfecta is a disturbance in the synthesis of type I collagen, which is the predominant protein of the extracellular matrix of most tissues. In bone, this defect of extracellular matrix causes osteoporosis, which leads to an increase in the tendency to fracture. Besides bone, type I collagen is also a major constituent of dentin, sclerae, ligaments, blood vessels, and skin; therefore, individuals with OI may also have abnormalities of these structures.
The process of collagen molecule formation starts with the synthesis of procollagen. This precursor consists of a long triple-helix protein flanked by 2 propeptides at its 2 terminals. Procollagen is synthesized and then secreted into the extracellular compartment, where the amino- and carboxy-terminal propeptides are cleaved; thus, the functional collagen molecule is formed. These molecules then assemble into an ordered fibril. Mutations that interfere with expression of the collagen gene, formation of the triple helix (amino acid sequencing), or procollagen secretion affect the structure and function of collagen fibrils, resulting in a form of OI.
Electron microscopic studies of OI demonstrate a decrease in the diameter of the collagen fibril, relative to the collagen fibril of healthy persons, and smaller-than-normal apatite crystals.
A number of genetic defects cause the abnormal type I collagen synthesis that leads to OI. OI generally arises from mutations in 1 of 2 genes that encode for the synthesis and/or structure of type I collagen: the COL1A1 gene on chromosome 17, and the COL1A2 gene on chromosome 7. Mutations in these genes may cause abnormal collagen to be produced and may lead to a decrease in the production of normal collagen. The varying degree to which these 2 factors manifest themselves results in the different phenotypic expressions of OI. Milder forms of OI are caused primarily by a decrease in production of normal collagen, whereas more severe forms are caused primarily by the production of abnormal collagen. These abnormalities may be dominantly inherited, or they may be the result of sporadic mutation.
Common causes of nonorthopedic morbidity in type I and type IV OI are joint hypermobility, which causes chronic joint pain, hearing impairment, and brainstem compression.Children with type III OI often require orthopedic care because of their progressive deformities. Standing and walking are often impossible because of spinal compression fractures and scoliosis. Progressive thoracic deformities are associated with recurrent pneumonias that often limit the patient's lifespan.


Type I: The life expectancy of patients with all forms of OI other than type III is often assumed to be shortened. However, according to Paterson et al, the life expectancy of patients with OI type IA is the same as that of the general population. Type IA is a subtype of type I OI in which dentinogenesis imperfecta (tooth abnormalities) does not occur. Type IB is a rare form of type I OI in which dentinogenesis imperfecta does occur. In types IB and IV, mortality is modestly increased in comparison with that of the general population; there is no statistically significant difference in life expectancy. Type II: This form of OI is fatal in the perinatal period.

Type III: Only in type III OI is life expectancy affected. However, patients with type III OI who survive beyond the age of 10 years have a better outlook than other patients with OI.
Osteogenesis imperfecta does not seem to have a predilection for any particular race. No known sex predilection is reported for osteogenesis imperfect. The onset of fractures and deformities varies according to the type of osteogenesis imperfecta (OI) that is present.
For type I, the age of onset is variable. This form most commonly appears during the preschool years when the child is starting to stand. Onset after puberty is uncommon, although fractures may recur in adulthood after menopause or after periods of inactivity, such as after childbirth. Type II occurs in utero. In type III, abnormalities are present at birth (ie, abnormalities develop in utero) in more than 50% of patients. Fractures are frequent during the first 2 years of life.Type IV abnormalities are present at birth in approximately 30% of patients. The onset of this form is during infancy or the preschool years.
The clinical features of osteogenesis imperfecta (OI) depend on the type, but bone fragility with multiple fractures and bony deformities are the common hallmark of all types.
The major presenting signs and symptoms of OI include blue sclerae, hearing loss, tooth abnormalities (dentinogenesis imperfecta), joint laxity, and abnormal skin texture (smooth and thin skin). Other features that are common to multiple OI types include bleeding diathesis (easy bruising) and respiratory distress.
OI is classified into 4 distinct types: I-IV. Some cases of OI do not fit easily into any of the 4 types. A type V category has been added to include patients with osteoporosis or interosseous membrane ossification of the forearms and legs, as well as patients who are prone to the development of hypertrophic calluses.




The type 1 prototypical and most common form of OI is associated with the best prognosis. The mode of inheritance is autosomal dominant. The distinguishing clinical features of type I are blue sclerae, which occurs in patients of all ages, and presenile conductive hearing loss; in addition, most patients with type I OI have a family history of hearing loss. Bone fragility is mild, and there are minimal bony deformities. The stature of patients with type I OI is often normal or near normal. Ligamentous hyperlaxity, resulting in joint hypermobility or subluxation, is common. Approximately 20% of patients have kyphoscoliosis.
Dentinogenesis imperfecta is present in some families but not in others.12 Therefore, type I OI is subclassified to distinguish patients without dentinogenesis imperfecta (type IA, more common) from those with dentinogenesis imperfecta (type IB, rare). Some investigators have suggested that these 2 subgroups are biochemically distinct and that individuals with OI type IB, whose bodies make structurally abnormal collagen, are more similar to those with OI type IV than to those with other types of OI, including type IA.
Type II is the most severe form of OI. It is characterized by extreme bone fragility that almost invariably leads to intrauterine or early infant death. The cause of death is most often respiratory failure. The mode of inheritance is autosomal recessive. The sclerae are blue and occasionally dark blue or black. Clinically distinguishing features include intrauterine growth retardation, thin and beaded ribs, crumpled long bones, and limited cranial and/or facial bone ossification. Limbs are short, curved, and angulated.
Type II OI can be further subdivided into types IIA, IIB, and IIC on the basis of the radiographic features of the long bones and ribs. Patients with type IIA or IIC inevitably die in the perinatal period; rarely, patients with type IIB survive into early childhood.
Type III is the next most severe form of OI after type II. It is the most severe form in which survival extends beyond the perinatal period.
Its hallmark feature is severe bone fragility and osteopenia, which is progressively deforming. The mode of inheritance is thought to be autosomal recessive. Multiple fractures and progressive deformity affect the long bones, skull, and spine and are often present at birth. Postnatal growth failure is severe. Kyphoscoliosis is common. Sclerae are either normal from birth, or they progress from pale blue in infancy to a normal appearance by adolescence.
Type III OI is probably the form that is best known to radiologists and orthopedic surgeons. Children with type II OI tend to have severe dwarfism caused by spinal compression fractures, limb deformities, and disruption of growth plates.
Type IV OI is distinguished from type I OI by the slightly increased, though still variable, severity of bone fragility and by the presence of normal sclerae. The mode of inheritance is autosomal dominant. Mild to moderate bony deformity of the long bones and spine is present; the incidence of fracture is variable. Basilar impression of the skull, with consequent brainstem compression, is common; it is reported in 70% of patients.


Hearing loss or a family history of hearing loss is noted in patients with this type of OI, as is dentinogenesis imperfecta. Type IV OI is also subclassified to distinguish patients without dentinogenesis imperfecta (type IVA) from those with it (type IVB). Compared with type I OI, hearing loss is less common in type IV, and dentinogenesis imperfecta (type IVB) is more common. Some authors have distinguished a self-limiting variant of OI, known as temporary brittle-bone disease. Its clinical features are identical with those found in cases of child abuse.
While there is no cure for osteogenesis imperfecta, there are opportunities to improve the child's quality of life. Treatment must be individualized and depends on the severity of the disease and the age of the patient. Care is provided by a team of health-care professionals, including several types of doctors, a physical therapist, a nurse-clinician and a social worker.
In most cases, treatment will be nonsurgical.
Medical bisphosphonates, given to the child either by mouth or intravenously, slow down bone resorption. In children with more-severe osteogenesis imperfecta, bisphosphonate treatment often decreases the number of fractures and bone pain. These medications must be administered by properly trained doctors and require close monitoring.
Casting, bracing, or splinting of fractures is necessary to immobilize the bone so that healing can occur. Movement and weight bearing are encouraged as soon as possible after fractures to increase mobility and decrease the risk of future fractures.
In surgical treatment, repeated fractures of the same bone, deformity, or fractures that do not heal properly are all indications that surgery may be necessary. Metal rods may be inserted in the long bones of the arms and legs. Some rods are a fixed length and must be replaced as the child grows. Other rods are designed like telescopes so they can expand along with the bone growth. However, other complications may occur with telescoping rods.
In many children with osteogenesis imperfecta, the number of times their bones fracture decreases significantly as they mature. However, osteogenesis imperfecta may become active again after menopause in women or after the age of 60 years in men. Scoliosis, or curvature of the spine, is a problem for many children with osteogenesis imperfecta. Bracing is the usual treatment for scoliosis, but it is often ineffective in children with osteogenesis imperfecta. Spinal fusion, in which the vertebrae are realigned and fused together, may be recommended to prevent excessive curvature.
At present there is no cure for OI. Treatment is aimed at increasing overall bone strength to prevent fracture and maintain mobility.
There have been many clinical trials performed with Fosamax (Alendronate), a drug used to treat women experiencing brittleness of bones due to osteoporosis. Higher levels of effectiveness apparently are to be seen in the pill form versus the IV form, but results seem inconclusive.

Bone infections are treated as and when they occur with the appropriate antibiotics and antiseptics.
Physiotherapy used to strengthen muscles and improve motility in a gentle manner, while minimizing the risk of fracture. This often involves hydrotherapy and the use of support cushions to improve posture. Individuals are encouraged to change positions regularly throughout the day in order to balance the muscles which are being used and the bones which are under pressure.
Children often develop a fear of trying new ways of moving due to movement being associated with pain. This can make physiotherapy difficult to administer to young children. With adaptive equipment such as crutches, wheelchairs, splints, grabbing arms, and/or modifications to the home many individuals with OI can obtain a significant degree of autonomy.
Spinal fusion can be performed to correct scoliosis, although the inherent bone fragility makes this operation more complex in OI patients. Surgery for basilar impressions can be carried out if pressure being exerted on the spinal cord and brain stem is causing neurological problems.
Because osteoporosis and multiple fractures are hallmark features of osteogenesis imperfecta (OI), other disorders that cause multiple fractures or decreased bone mineralization may be considered in the differential diagnosis. Such disorders including juvenile osteoporosis, steroid-induced osteoporosis, menkes (kinky-hair) syndrome, hypophosphatasia, battered child syndrome (syndrome X), temporary brittle-bone disease.

References:
http://emedicine.medscape.com/article/947588-overview

http://emedicine.medscape.com/article/411919-overview

http://ghr.nlm.nih.gov/condition=osteogenesisimperfecta

http://orthoinfo.aaos.org/topic.cfm?topic=A00051

http://hwmaint.jmg.bmj.com/cgi/content/abstract/16/2/101

N.B.: This article is excerpted from the book MUSCULOSKELETAL INJURIES for UNDERGRADUATES