Bence Jones Protein

The Bence-Jones protein (BJP) was described in 1962 as “free monoclonal light chains”, synthesized by a

single clone of B cells. Normal plasma cells appear to produce a slight excess of light chains, but B cell neoplasms may produce a much greater excess.

Once the mechanism of tubular reabsorption becomes saturated, BJPs are excreted in urine.

The molecular mass of BJP is quite variable; BJPs appear in urine as monomers (22 kDa), dimers (44 kDa), or low-molecular mass fragments (5–18 kDa), or show a high degree of polymerization.

Associated Diseases

The most frequent associations are with the following:

  1. multiple myeloma,
  2. Waldenström’s macroglobulinemia,
  3. monoclonal light chain-related amyloidosis (AL),and
  4. light chain deposition disease

Clinical Utility

BJP determinations are useful in the following (3):

  • Subjects with serum monoclonal component (MC): at diagnosis and during follow-up.
  • Patients suspected of having a monoclonal gammopathy, clinically or from laboratory findings as follows:

– bone pain, fatigue, recurrent infections, purpura, edema,

– unexpected hypogammaglobulinemia in adults, unexplained increased erythrocyte sedimentation rate, anemia, leukopenia, and thrombocytopenia, proteinuria

Detection

Sample

  • The College of American Pathologists issued guidelines defining the methods for BJP detection and quantification based on a 24-hour urine specimen.
  • However, 24-hour collections are cumbersome and er-ratic, and BJP is particularly prone to bacterial degradation.
  • The latter can be minimized by adding an antibacterial agent.
  • Considering these drawbacks, we recommend the use of the second morning void and expressing the concentration of BJP relative to urinary creatinine.
  • If the method in use is sensitive enough, the urine can be used unconcentrated; when the greatest sensitivity of BJP detection is clinically needed, urine should be concentrated.
  • In such case, the membrane used in the concentrating devices should have a cut-off preferably of 5 kDa and, in any case, less than 10 kDa.

Method

  • The chosen method should verify that the two fundamental characteristics of the LCs are present: e., that they are free and monoclonal.
  • Immunofixation combines an electrophoretic step to verify the molecular homogeneity of the protein with immunologic typing,it is the recommended method for BJP detection.
  • Antisera to KIEκ and LAMBDA LCs together with antiserum to the heavy chain (HC) of the serum monoclonal immunoglobulin should be used.
  • Antisera to free light chains (FLCs) are expensive; in addition, they are often nonspecific and can have low avidity.
  • They can be useful only if it is suspected that a BJP is co-migrating with an intact immunoglobulin.
  • This suspicion is raised when there is a discrepancy between the HC and the LC signal grossly in favor of the latter

Sensitivity

  • The indication of a detection limit for BJP can only be approximate since there is no way of obtaining an accurate quantification of the protein.
  • However, since the indicated amount for polyclonal LC excretion is approximately 10 mg/l, a method with a sensitivity down to this limit is suggested.
  • Among the sensitive stains, colloidal gold provides the highest sensitivity (1–2 mg/l); colloidal Coomassie stain can detect BJP at 10 mg/l or less

Interpretation

  • Using methods of high resolution and adequate sensitivity, the appearance of so-called LC ladder patterns is common.
  • These multiple, evenly-spaced bands have been well described and are the consequence of the excretion

of polyclonal LCs in individuals with impaired tubular reabsorption.

  • The pattern is typical, and an experienced eye can distinguish them from BJP; however, it may sometimes be difficult to identify a BJP band co-migrating with one of the multiple bands

 Alternative approaches

  • Immunochemical methods (nephelometry, turbidimetry) for the quantification of FLCs in urine can be used for BJP detection as an initial screening to exclude BJP, thus reducing the number of samples to process further.However, the amount of BJP can range from a few milligrams to grams per liter, so that the assay can eas-ily fall into the antigen excess zone.
  • Therefore, it is mandatory to control and avoid antigen excess and to document a detection limit below 10 mg/l.
  • A positive test should be followed by immunofixation (IF) for the following reasons:
    • If the antisera used in the immunochemical method are against LCs (free and bound) it is necessary to document that the LCs are free;
    • Since FLC antiserum is incapable of distinguishing monoclonal from polyclonal LCs it is necessary to define the clonality. Although in LC multiple myeloma the synthesis of polyclonal LCs is usually depressed, in several other clinically important instances (AL, LCDDs) the concentration of polyclonal FLCs in urine can be significant and variable in the course of the disease;
    • IF is presently recommended to define the response to high-dose chemotherapy in multiple myeloma. It has been shown that patients achieving a negative IF have the best prognosis; accordingly, therapeutic strategies are presently designed to achieve negative IF.
  • The cost-benefit ratio of screening samples for BJP using quantitative immunochemical methods should be carefully evaluated depending on the type of population to be examined and the analytical performance of the immunochemical method used.

Tests to be discouraged

  1. Methods for measuring total proteins in urine (both precipitating and dye-binding) are insensitive and not accurate for detecting BJP.
  2. Dipsticks used to screen for protein in the standard urine examination are impregnated with a buffered dye which is sensitive mainly to albumin and can completely miss the presence of BJP.
  3. The unreliable heat test is mentioned only because of its historical value since not all BJP precipitate upon heating.

 

Quantification

  • Several staging systems, definitions of indolent disease and treatment guidelines for multiple myeloma and related conditions, are based on decision levels of BJP 24-hour excretion.
  • However, none of these studies specifies how to identify and measure “something called BJP”.
  • The clinical value of BJP quantification is limited by metabolic and analytical problems.
  • The excretion of BJP is influenced by its degree of polymerization, by renal function, and by the deposition rate of the protein in different tissues, so the amount of BJP in urine is not directly related to the tumor cell mass.
  • Again, an accurate measurement of BJP cannot be easily achieved with present laboratory techniques.
  • The guidelines of the College of American Pathologists suggest the following procedure:
  1. Measurement of total protein in a 24-hour specimen;
  2. Electrophoresis and IF of concentrated urine to detect BJP;
  3. Densitometric scan of the BJP peak; and
  4. Determination of the ratio of the BJP peak percentageto the total protein.
  • This procedure has some drawbacks:

– Inaccuracy of the methods in use to measure total protein in urine: these methods  are often insensitive to microproteins in general and to BJP in particular.However, if the urine electrophoresis shows that BJP constitutes almost all urinary protein excretion, the determination of total urinary protein performed in the same laboratory by the same method at two points in time may provide useful indications regarding the efficacy of therapy;

– Different proteins can have different affinities for the dyes used to stain electrophoretic strips, and thus a lack of linearity of the densitometric response can be observed;

– Quite often multiple bands of BJP are present in the urine or the BJP co-migrates with other proteins, so that it is difficult to delimit the BJP peak correctly by densitometry.

It is suggested that follow-up of patients be performed in the same laboratory in order to minimize analytical variability.

  • Immunochemical methods using antisera against FLCs have the drawbacks listed in the “Alternative approach”
  • Moreover:

– Antisera raised against a polyclonal mixture of LCs do not necessarily react in the same way with the monoclonal LCs of the sample;

– The molecular mass of BJP is quite variable; in urine, they appear as monomers (22 kDa), dimers (44 kDa), low molecular mass fragments, or can show a high degree of polymerization. The state of aggregation/ fragmentation of FLCs in urine is highly variable and unpredictable, depending on many. In addition, the antisera used for the quantification of FLCs are directed against epitopesthat are hidden in whole immunoglobulin molecules. In some severe conditions, such as AL, LC fragments of 5-18 kDa, comprising the amino-terminal region, are present in serum and urine and are the main constituents of amyloid fibrils. These pathogenic LC fragments can lack some or all relevant epitopes and be poorly recognized, or missed, by the antisera. All these factors can influence the immune reaction and may invalidate the calibration making the quantification of urinary monoclonal LC unreliable;

– The precision of the quantitative methods at the extremes of the dynamic range  is poorly defined;

– There is no reference material for monoclonal LCs,and accuracy therefore remains an open problem;

– There is no standardization of the several methods available for the quantification of urine FLCs.

  • Results could differ significantly between methods; this represents a serious problem in consideration of the present extreme mobility of patients.
  • Despite all these drawbacks, the immunochemical estimation of BJP may be of clinical value to monitor the clone during treatment, but it is necessary to utilize the same antisera and calibrators throughout the followup and to keep in mind all the caveats listed above.
  • Recently, it has been reported that in LC myeloma the quantification of FLCs in serum by nephelometry
  • correlates with changes in urinary FLC excretion.
  • The authors suggest that serum measurements may be an alternative to the cumbersome 24-hour urine collections in monitoring patients with LC myeloma. However, more data are needed before considering this alternative.

INSTRUCTIONS TO BE FOLLOWED AFTER EXTRACTION

INSTRUCTIONS TO BE FOLLOWED AFTER EXTRACTION :

 EXTRACTION 

Definition

Extraction is defined as complete, painless removal of tooth or tooth root with minimal trauma to surrounding investing structures, so that the wound heals uneventfully and there will be no post operative prosthetic problems”. extraction

POSTOPERATIVE INSTRUCTIONS 

  1. Your dentist will place a cotton or gaze roll in the area of tooth extraction, which need to be hold or bite firmly so that it creates a pressure over the surgical or extracted tooth site for 30min. There is no need of replacing the cotton again unless you note an active bleeding from the site. If you notice any active bleeding after 30min consult your dentist immediately.guaze pack
  2. After you remove the cotton from your mouth have some cold things like ice-cream such that it come in contact with the extracted site  icecream after extraction
  3. You are advised not to spit for the next 24 hours whether it might be your saliva or blood everything need to be swallowed, as spitting may create a negative pressure over the extracted tooth site and may initiate bleeding no spitting
  4. you are not allowed to gargle for next 24 hours. Gargling may cause disintegration of the blood clot and may initiate bleeding from the extracted socket. dont gargle
  5. You are advised not to touch the area of extracted site either with your tongue or finger
  6. You are advised not to have any hot food or beverages avoid hot food and beverages
  7. You are advised to have only cold and soft food icold food
  8. You are advised for Application of ice pack ice pack
  9. Avoid spicy and hard food items for next 24 hours  hot food
  10. Avoid eating from the side where your tooth was  extracted
  11. After extraction chances of swelling is quite common, in such case don’t panic swelling comes down slowly as healing progresses.
  12. Avoid hot fermentation on the side of extraction  hot fermentation
  13. Avoid hot food or beverages for next 24 hours. avoid hot food and beverages
  14. You are advised not to skip antibiotic and analgesic medication prescribed by your dentist
  15. You are advised to visit your dentist after one week for suture removal ( If sutures are placed) suture removal
  16. You are advised to avoid smoking, consumption of alcohol and use of tobacco for next 48 hours quit smoking,alcohol
  17. You are advised to restrict your self to calm activities ( Avoid vigorous exercise for next 48 hours) avoid workout
  18. If bleeding persists even after 24 hours immediately contact your dentist consult dentist

MANAGEMENT OF THE DENTAL OFFICE

Successful practice is a result of proper management of resources, professional skills, and relationships with other health care providers and public in general. In India, commoners are largely dependent mainly on government health care delivery systems in which dental services are integrated with medical services, while the affluent get private services for a fee. In recent years, policies of the government have allowed the participation of individual and multinational groups in private health care systems. Dental requirements of the public in India are vast, varying and largely unmet

  • FRONT OFFICE PERSONNEL:
    • The dentist may appoint a full time receptionist, a dental chair side assistant or a person who can do both the work and also part time personnel who will clean the floor, equipments etc.,
    • The front office staff plays a vital role in the success of the practice. The receptionist should be able to handle all kinds of patients
    • Receptionist should be the liaison between the dentist and patients. While giving appointments she should know the approximate time required for each treatment. She should be able to rearrange the appointments if such a situation emerges that the patient flow is regularly maintained without wasting any time
  • INTERIORS:
    • The furniture in the reception area must be durable, esthetic and comfortable. It should neither be too cheap nor be excessively lavish
    • It is better to have a sound proof operatory, atleast with the pediatric population in mind. A second waiting area between the reception and operatory may be incorporated
    • Electrical connection must be concealed and designed keeping in mind the lighting, fan, exhaust, compressor, x- ray unit, computer, dental chair and music system
    • The drainage connection must be designed to aid conduction of plumbing work with proper slopes for drainage etc., to avoid water stagnation in the pipelines and further inconvenience
    • The floor and walls should be designed considering the esthetics. Design should be such that there is minimum possibility of dust accumulation. Rubberized vinyl flooring is advised as it is easy to keep clean
    • A separate x- ray room with wall enclosed in a lead barrier will help to minimize x-ray hazards
    • Autoclaving and sterilization may be carried out in a separate chamber, close to the work area
  • APPOINTMENTS:
    • If a dental clinic is located close to government, commercial offices, corporate and business houses, the appointments are generally to be given in between 9.30 AM to 6 PM because most employees would like to avail treatment by taking permissible short break from their offices
    • If the clinic is in a residential area, the appointments are generally fixed between 8.30AM to 12. 30PM and 4.30PM to 8. 30PM, because in the morning office goers can visit the dentist before going to the office, while the house wife can avail treatment after 10 AM, retired and old people can visit the dentist by 11AM children will be brought from school by 4.30 PM and the office goers can also come for treatment after 6PM from office
    • Preferably, A diary has to be kept to note appointments so that there is no confusion over the appointments
    • Patients should be scheduled to arrive atleast 15minutes before the scheduled appointment
    • If possible the front office assistant should be trained to call each patient atleast half an hour before the appointment and confirm the appointment. This also could act as a reminder for the patient regarding his/ her appointment
  • STOCK AND MATERIALS:
    • For the smooth functioning of the clinic, the assistant or the receptionist should have good knowledge about the materials used in the clinic
    • The staff working in the clinic should know the amount of material required for a particular period, amount of material in the stock, quantity to order, from where to purchase, the mode of payment etc.,
    • Care should be taken to have sufficient material in the stock, so that the routine work doesn’t get disturbed. Material should never be bought in excess than required for a particular period as most of them have a short shelf life
    • The dental office should know how to make economical use of the materials
  • RECORDS AND ACCOUNTING:
    • Maintanance of clinical records is a must and should be kept confidential. They not only serve as a basis for future treatment, but also as evidence in case of legal claims or when summoned by law
    • Accounting includes:
      • Income generated
      • Expenses met
      • Tax paid
      • Interest on loans
      • Membership fee for associations
      • Professional indemnity etc.,
    • The dentist himself or his/ her assistant can do accounting, but by preference should be done by a qualified auditor
  • MEASURE OF SUCCESS IN PRACTICE:
    • ‘Success’ is a relative term
    • A dentist who is well known and respected by his/ her fraternity for his/ her professionalism, loved by his/ her patients for his/ her concern, kindness and devoted work, when his/ her absence is felt- are some of the indicators of success
  • WASTE MANAGEMENT AND INFECTION CONTROL:
    • Wastes have to be segregated before disposal
    • Wastes that are hazardous may be disposed through companies that collect biomedical wastes and process them
    • A tie up may be made with the nearest hospital to dispose wastes that are to be incinerated
    • It is important to follow suitable infection control measures to prevent cross infection
    • The dental assistant may be taught the use of an autoclave so that he/ she sterilizes instruments on time
    • Hand washing between patients not only protects the clinician from cross infection but also gives the patient a sense of comfort and increases the confidence of the patient on the dentist
    • The parts of the chair that are generally contacted like the light handle etc., may be wrapped with a polythene sheet or aluminum foil, which may be replaced between patients
    • Use of a head cap, face mask and gloves help prevent contracting infection from the patient
  • GROWTH AND EXPANSION:
    • Related directly to the ability of the dentist to deliver thorough performance
    • It is the measure of popularity achieved and monetary status achieved over a period of time
    • Expansion is the extension of the operatory and inclusion of qualified associates into practice
  • MISCELLANEOUS:
    • Dentist should have good communication skills.
    • In the first visit itself, a detailed history must be obtained and the condition explained along with the approximate cost and mode of payment for the treatment
    • It is a good practice to open the clinic atleast half an hour before the first appointment. The assistant must arrange instruments for each appointment at the right time
    • Preferably, written instructions have to be given- it saves time
    • It is better to have a link with credit card managers
    • If possible an attachment to an insurance company or joining the medical panel of the company may be tried for
    • The dentist should have an association with a good laboratory which promptly delivers the work on time
    • Arrangement for proper waste disposal must be made
    • All the professionals also need an occasional rest from work. A dental practitioner must take one day off from work every week, should have atleast 2 vacations every year to spend time with the family
    • Whenever the dentist plans such holidays, alternative arrangements may be made to reduce inconvenience to the patients.

REFERENCES:

  • Essentials of Preventive and Community Dentistry- Soben Peter- 3rd Edition
  • Textbook of Preventive and Community Dentistry- S S Hiremath- 1st Edition
  • Essentials of Preventive and Community Dentistry- Soben Peter- 4th Edition

 

Thyroid Gland

Introduction :

  • Thyroid gland lies deep to the sternothyroid muscle and sternohyoid muscle.
  •  Thyroid gland is located anteriorly in the neck at the level of C5 – T1 vertebrae.
  • Thyroid gland consists of right and left lobes connected by “Isthmus”.
  • Right and left lobes are located anterolateral to the larynx and trachea.
  • Isthmus is located over the trachea usually anterior to the second and third tracheal ring

thyroid gland.

  • Thyroid Gland is surrounded by a thin fibrous capsule.
  • Thyroid Gland has a dense connective tissue which connects the capsule to the cricoid cartilage and to the superior tracheal ring.
  • External to the capsule there is a loose sheath formed by the pretracheal layer of deep cervical fascia.

VASCULAR SUPPLY :

Arteries :

  1. Superior thyroid artery
  2. Inferior thyroid artery

  • Thyroid Gland  is highly vascular and is supplied by Superior thyroid Artery and Inferior thyroid artery which lies between the capsule and the pretracheal layer.
  • Superior thyroid artery descends to the superior poles of the thyroid gland, pierces the pretracheal layer and divides into anterior and posterior branches to supply anteriosuperior part of the gland.
  • Inferior thyroid artery is the largest branch of the thyrocervical trunk, it runs superiomedially posterior to the carotid sheath and reaches the posterior aspect of the thyroid gland.
  • They divide into several branches and pierces the pretracheal layer and supply the posterioinferior aspect of the gland and inferior poles of the thyroid gland.
  • The right and left superior thyroid artery and inferior thyroid artery anastamose  with each other with i the gland.

VEINS :

  1. Superior thyroid vein
  2. Middle thyroid vein
  3. Inferior thyroid vein+

  • Thyroid Gland is drained by 3 pairs of veins from the thyroid plexus of veins on the anterior surface of the gland anterior to the trachea.
  • Superior thyroid veins accompanies superior thyroid artery and drain the superior poles
  • Middle thyroid vein courses parallel to the inferior thyroid artery and drains the middle of the lobes.
  • Inferior thyroid vein drains the inferior poles.
  • Superior thyroid veins and middle thyroid vein drains into inferior juglar vein
  •  Inferior thyroid vein drains into brachiocephalic veins

LYMPHATIC DRAINAGE :

  • The lymphatic vessels of the thyroid gland run in the interlobular connective tissue, they communicate with the capsular network of lymphatic vessels.
  • From the capsular network they pass first to the prelaryngeal lymphnodes, pretracheal lymph nodes and paratracheal lymphnodes whic in turn drains into superior deep cervical lymph nodes and inferior deep cervical lymph nodes.
  • Laterally, lymphatic vessels located along the superior thyroid vein pass directly to the inferior deep cervical lymph nodes.
  • some of the lymphatic vessels may drain into brachiocephaliclymph nodes or thoracic duct

NERVES : 

These are derived from Superior cervical sympathetic ganglion, middle cervical sympathetic ganglion, inferior cervical sympathetic ganglion.. they reach the gland through superior thyroid periarterial plexuses and inferior thyroid periarterial plexuses that accompany the thyroid arteries.