|Year : 2022 | Volume
| Issue : 1 | Page : 17-21
Acute leukemia and its identification in ayurveda - A review based on clinical observations
Department of Research in Indian Medicine, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India
|Date of Submission||12-Nov-2021|
|Date of Decision||24-Apr-2022|
|Date of Acceptance||07-Jun-2022|
|Date of Web Publication||22-Aug-2022|
Dr. B V Kumaraswamy
Department of Research in Indian Medicine, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka
Source of Support: None, Conflict of Interest: None
Modern science and medicine established scientific details of leukemia only during the second half of 19th c. J. H. Bennett a pathologist established leukemia by publishing study on 35 cases and he is credited with the innovation of leukemia; in Ayurveda no systematic study seems to have been attempted to understand or identify the leukemia let alone the treatment. This was also due to the lack of opportunities in oncology institutes or organized research by government bodies. Extensive research on all aspects is underway in modern medicine and claims are being made by many traditional healers, but no system of medicine has been able to achieve success so far; experts in Ayurvedic system say the strategies do hold promising positive results but needs proper studies. Here an attempt has been made to understand and identify leukemia by clinically studying well diagnosed cases for 11 years in collaboration with oncology experts in a premier Onco-institute of India. Study involved 800 patients who were clinically studied from an Ayurvedic perspective during their entire course of disease with or without treatment; detailed descriptions and analysis of various possibilities in the Ayurvedic system were discussed (and documented) and finally concluded based on authoritative sources.
Keywords: Acute Leukemia, Ayurveda, Jwara, Pandu, Raktapitta, Review, Shosha, Udara, Visha
|How to cite this article:|
Kumaraswamy B V. Acute leukemia and its identification in ayurveda - A review based on clinical observations. J Integr Health Sci 2022;10:17-21
|How to cite this URL:|
Kumaraswamy B V. Acute leukemia and its identification in ayurveda - A review based on clinical observations. J Integr Health Sci [serial online] 2022 [cited 2022 Oct 2];10:17-21. Available from: https://www.jihs.in/text.asp?2022/10/1/17/354232
| Introduction|| |
Cancer has become a major challenge and concern for biologists and physicians not only due to problems in treatment but more so due to its increased prevalence worldwide. The growing knowledge about the nature of the disease with the help of modern science and technology has not been translated to great benefits in control or treatment. With significant improvement in treatment and prevention of cardiovascular diseases, cancer has or will soon become the number one killer in many parts of the world. Nevertheless, tremendous progress has been made in understanding the complex pathological process and thus the diagnosis of cancer seldom remain speculative. In order to understand cancer, leukemias in particular, in its proper perspective, and then in the context of Ayurveda, there have not been serious attempts due to innate difficulties. In addition, despite advances in oncology, Ayurveda physicians remain isolated in their understanding of cancer. Modern medical pathology has taken a quantum leap in precise diagnosis of leukemias, especially with developments in human genetics. The scientific researches in the field of medicine and other allied systems have not been very rewarding to Ayurveda. The difficulties mainly relate to the problem of arriving at a diagnosis due to the absence of definitive methods and facilities for such studies. Clinical knowledge however excellent always demands objective verification (Pratyaksha Pareeksha). Sensory perception is highly susceptible for various kinds of bias and thus pose a major limitation. The Anumana (inference) which ultimately helps in final decision-making depends on the sensory data. If the information thus obtained is objective and refined, the efficiency in diagnosis with the detailed analysis of its involved components will increase.
In 1952 a pathologist named Bennett described this phenomenon in 35 patients, which opened a new era in modern pathology. Malignancy is now strictly and exclusively a genetic phenomenon. This pathology is highly subtle and understandable only by microscopic studies. It occurs through a sequence of events beginning at the tissue level and eventually reaching multiple organs and death. This natural history is common in all cancers but originates in different tissues. Leukemia or hematological malignancy is one such situation commonly seen in medical oncology unit which naturally attracted the attention. Diagnosis of these cases appeared as a prime important factor in addition to understanding the pathological process. In this paper, two types of leukemias are presented (1) acute myeloid leukemia (AML) and (2) acute lymphocytic leukemia (ALL).
| Objectives|| |
Understanding AML and ALL from the perspective of Ayurveda.
| Materials and Methods|| |
A total of 800 cases (from 1986 to 1997) were studied and documented from prediagnostic stage, during treatment and while on follow-up. All confirmed cases of acute leukemia were included in the study. These patients were thoroughly examined and relevant clinical data were obtained as per the Ayurvedic methods. Modern objective criteria were used for the final diagnosis, including hematological, cytochemical, and cytogenetic methods; these were taken as the basis for identification and classification of different types of leukemia. At all levels of follow-up, medical oncologists responsible for the case and professors were consulted for objective assessment of clinical parameters.
| Leukemia-Clinical Work and Observation|| |
During the entire study period, all registered cases of pediatric and adult were examined very closely to study the varieties of clinical situations. Each of these cases was specifically examined and possible Ayurveda diagnosis was tried which was completely based on Lakshanas (symptomatology) and Pareeksha (clinical examination) and Rogi-ithihasa (patient's history). Three Ayurvedic methods of Pratyaksha (direct examination)-Anumana (inference) and Aaptopadesha (learnt by teaching and referring texts) were adopted; the information was further subjected to three processes for subjective verification; Chintana (logical thinking), Manana (analytical processing), and Nidhhyasana (to meditate consciously) routinely.
Leukemia is a common malignancy affecting both children and adults, caused by changes in normal cell regulation processes resulting in an uncontrolled proliferation of hematopoietic stem cells in bone marrow. Although all leukemias originate from the malignant stem cells of the bone marrow, the disease manifestation has wide spectrum of clinical presentation. They differ in terms of etiology, age, onset, symptoms, prognosis, severity, response to treatment, etc., Hence in spite of the involvement of cells of the blood is common, all leukemias cannot be considered as one entity. Observing both acute myeloid and lymphoid leukemia cases of children and adults, Ayurvedic principles were applied to arrive at a diagnosis. During this time, 5 differential diagnosis (Jwara, Raktapitta, Shosha, Pandu, and Udara) were considered as possibilities, but none of these were convincing with the observed clinical picture. It was clear that leukemias does not fit into any of the well-known disease entities.
Acute leukemia cases are really “Acute” in the true sense of the term. The AML is known to be more common in adults and ALL in children. ALL is essentially a childhood disease and with the modern chemotherapy and excellent supportive care it is now regarded as a curable malignancy. Conventionally, both of these leukemias start with onset of fever (Sannipata-jwara-fever having involvement of three Doshas), progressive weakness, followed by significant pallor within 2–3 days. All these will progressively develop into a frightening situation for both patient and caregivers. Bleeding also manifests faster in AML than in ALL, and many other signs and symptoms will also be present but cannot be regarded definitively as their incidence varies greatly; almost all of these symptoms are caused by infections caused by the severely weakened immune system. Hepatomegaly and splenomegaly are not significant in AML; but in ALL, it was observed as predominant clinical finding. Respiratory and gastrointestinal tract infections were the most common. Bleeding and infections are the common cause of death in these two types of leukemias.
| Ayurvedic Clinical Diagnosis|| |
After systemic study of 800 cases of leukemias, five differential diagnoses were considered.
Panduta (pallor or anemia) of varying degrees is the most important sign of both types of leukemias, but the history is very short and the disease progression is fast, and when patients bleed, it becomes severe. Panduroga found in texts do not explain acuteness and Jwara is not a main Lakshanas except in Pittaja Jwara, Raktasrava (bleeding) is also not a Lakshanas essentially it is a chronic disorder and progresses to Kamala (~jaundice). The other two conditions mentioned are Kumbhakamala and Haleemaka which are found in chronic progressive process are characterized by color changes in the skin; but leukemias are associated with high degree fever and progresses to bleeding and death and not chronic at all. Although Jaundice occurs in 60% of cases most of them recover completely, and mostly viral infections or due to Hepato-toxicity of drugs. The descriptions of hematuria, melena, hematemesis, etc., are seen in Kamala also, but they all presupposes the presence of Kamala which is not the situation in leukemia at all. Jaundice at the most can be regarded as a manageable complication (Upadrava) however, in some cases it can cause death also. Due to the treatment of ALL, death mainly occurs due to hepatic failure; since all ALL patients are treated, their life is prolonged. In addition, jaundice can develop due to immune suppression caused by the disease or hepatotoxicity caused by the drugs. The untreated cases will die so fast that there is hardly any time for Kamala (jaundice) to develop. Hence, both AML and ALL cannot be taken as Pandu Roga.
This is a disease in which bleeding is one of the main characteristic symptoms. Bleeding occurs in both AML and ALL either in the beginning itself or in the advanced stage; pallor has been described in the texts as an Upadrava, obviously as a consequence of bleeding. However, the Upadravas of Raktapitta mentioned in texts can be appreciated in leukemias from the beginning itself. Since bleeding is a Pratyatma Lakshana (main symptom) of this disease (more than 50% cases in this study did not had bleeding on presentation) and complete absence of Poorvaroopa, and fever being excluded as a Lakshanas, the possibility of Raktapitta is ruled out; it can be taken as Raktasrava or bleeding which is a terminal stage of leukemias. Further the presence of lymph nodes and hepato-splenomegaly which is very significant in ALL and less significant in AML are not mentioned in Raktapitta.
Shosha or Rajayakshma
Shosha was considered as one of the possibilities because (i) it is the main disease associated with Ojas-and Dhatu Kshaya or immunodeficiency. (ii) Textual explanations show fever and bleeding as two important Lakshanas. In general, Shosha is taken as tuberculosis, but when we study the textual details, it is obvious that all immunodeficiency disorders are to be considered under this category as Dhatukshaya (tissue emaciation or loss) is predominant. Both AML and ALL patients develop weakness but Dhatukshaya are not predominant except Rakta Dhatu, but all other Lakshanas of Shosha viz., Jwara, Kasa, etc., were clearly seen in leukemia cases. The acute onset and progressive pallor seen in leukemias are not found in Shosha; although pallor can occur in progressive diseases due to loss of blood or Dhatukshaya, the description of Shosha clearly indicates that it is not an acute disorder but it is a consequence of Dhatukshaya as a chronic process. AML and ALL can produce Shosha as a consequence which is observable mainly due to Rakta Kshaya, it cannot be in the sense of wasting. However, in the natural history of leukemias, hepatosplenomegaly, severe anemia, and bleeding from all orifices and skin changes develop very fast and untreated patient succumbs to death in the short period which is not so in Shosha. Since immunodeficiency is common in both it is desirable to consider Shosha as an Upadrava of leukemia than equating with the disease proper. Shosha is undoubtedly a chronic disorder and even without treatment patient survives for longer periods.
Ayurveda has given great importance to fevers in general and Sannipata Jwara in particular, hence it was considered in leukemias due to presence of high degree intermittent fever as a main presenting symptom. There are many references in Ayurvedic texts to this as a high degree fever. In leukemia, the fever is typically high and is usually accompanied by pallor, especially in children. On examination, lymph node enlargement and hepato-splenomegaly are noted; these two advances rapidly along with pallor; in 30%–40% of cases, bleeding symptoms occur. AML in adults clinically present mainly fever with bleeding manifestations. Sannipata Jwara is described to be of many types and although Jwara is present in all cases the clinical picture of leukemia especially in children do not match at all. Texts describe only two Lakshanas which are found occasionally. (1) Rakta stheevana (hemoptysis), and (2) Rakta-shyava Kotha (bluish red eruptions) are noticeable. But both are transient and not significant contrarily here Raktasrava occurs; the most dominant clinical finding of lymphadenopathy and organomegaly are not described in texts. Even in myeloid leukemia of adult's only fever matches and hence cannot be considered. Prognostically, the natural history in both AML and ALL is similar but symptomatically differ clearly. Ayurveda texts do not explain bleeding as the significant Lakshana in progressive disease. Splenic and hepatic enlargements were essentially due to the accumulation of excessive leukemic cells and not of any primary pathology; further it was also observed that reversing of organomegaly was very fast during treatment. The Jwara and Yakrut-Pleeha Vriddhi were symptoms only and not Vyadhi per say. There was almost a consensus mental frame to take adult leukemias AML under Sannipata Jwara and 10 cases were separately studied with very close observation and examination with special arrangement. Finally, the clinically significant factor of anemia with bleeding which completely reverses by blood transfusion alone led to the conclusion of a pathology different from Sannipata Jwara. Jwara in leukemia cases can be differentiated only by long-time experience; this long-term clinical experience with large numbers clearly ruled out this possibility.
This is explained in discussion.
| Discussion|| |
During the study, observations clearly lead to the conclusion that leukemia is not a disease entity that can be equated with any of the usually recognizable diseases mentioned in Ayurveda literature. However, the observations lead to the confidence of the fact that it must have been mentioned in some context or the other. Continuing with clinical observations, the sequence of events with the leukemia patients and the modern epidemiological studies emphasizing the etiology of the man-made chemical environment and allied factors led to think about the possibility of Visha-Janya-Roga (diseases caused by poisonous substances). The unique concept of Garavisha (artificial poison) mentioned in the texts producing various problems and its close resemblance with innumerable toxins and chemicals affecting the environment increasingly co-related to identify leukemias with Vishas. The Vishas, irrespective of the source has been described as to possess qualities opposite of Ojus, and attacks the Rakta Dhatu., Ojus is a very important and unique substance mentioned in Ayurveda as an essence of all body elements and gives the vital energy and helps in maintaining positive strength and integrity of the whole being. Currently, it can be partly understood under the immune system. It can only be identified subjectively by experience and in leukemias, it is very obvious and can be taken as a vital symptom.
The Garavisha is descried as a unique type of occult material that vitiates primarily the blood in such a way that it produces an irreparable damage resulting in a clinical situation which correlates with present understanding of acute leukemias. It is undoubtedly true that Vaidyas in ancient times recognized this concept, which was an excellent development of the founder fathers of Ayurveda.
AML particularly has been well known to be caused by chemical carcinogens.,, Benzene and many hydrocarbons, and therapeutic drugs including anti-cancerous agents have been implicated as carcinogenic agents.,, These are only a few on which evidence is available, for the vast majority of substances in our daily life, agriculture and horticulture (indiscriminate use of pesticides, fertilizers) poultry, industries etc.; also, in the environment, the data is accumulating fast and looks frightening. Scientifically, they are well known to be toxic to living beings depending on the quantity of exposure. The 20th century has seen the creation of a modern world dominated by chemical-based environment virtually encompassing the world. The entire animal and human lives do not have easy escape even in the outer space which is increasingly being recognized as “an ironically suicidal contribution to the self.” The bone marrow, which is the seat of very vital elements of life, produces all the blood cells is very subtle and highly susceptible to toxicity of chemicals and drugs. Most of the inorganic substances of industrial world poses danger to the core of 'genetic material 'of Bone marrow resulting in genetic predisposition and malignant possibilities.
The toxic chemicals and drugs that have no food value in the Ayurvedic framework are classified as Dooshivisha which are low-grade inorganic substances, and some as Garavisha which are high-grade chemical and biological substances. Ancient texts refer to Garavisha as an artificially made poison. Since the source material for this is not fixed and clear the effects also vary. However, conceptual descriptions correlate to manmade innumerable bio-toxic chemicals alien to animals and humans referred as “carcinogenic” can be considered under this.
With the current lifestyle, humans are primarily exposed to synthetic chemicals available in innumerable forms. In rural areas, the hazard of pesticides, fertilizers, etc., (many of them could be carcinogenic) is quite extensive (mainly due to lack of awareness) and the malnutrition and infections may add to the problem. The accidental consumption of these chemicals in agriculture during storage, contamination due to ignorant handling is very common. Now, it is well known that in India the traces of these chemicals are found in milk and its products, vegetables and food grains and fruits., Man-made environment has created toxic assault to living beings virtually in all the spheres of life. Renal toxicity, hepatic toxicity, immune suppression, brain damage, and bone marrow toxicity are some of established hazards known to occur due to toxic chemicals.,,, Many of these toxic chemicals may also initiate processes in the body which in turn produce genotoxicity and mutations leading to leukemia. Ayurveda further describes the incompatible food ingredients, preparing methods, combinations, etc., Some of them act potentially like Garavisha.
Dooshivisha is another type of poison described by all the original texts of Ayurveda responsible as a causative factor of serious deceases. The name ”Dooshi”is similar to as Dosha and has similar characteristic feature as an etiologic factor also. The Dooshivisha described as “by passer” of the Tridoshas and vitiates the Dhatus directly. This can result in symptoms like Ardita (facial palsy), tremors, loose-colored stools, disorders of the blood, thirst, loss of taste, unconsciousness, nausea, and vomiting. and further it can lead to the disease Dooshyodara as clearly described by Sushruta.
The descriptions given in the text shows that Dooshivisha related disorders needs to be considered separately for both diagnosis and treatment. In such situations, the usual methods of treatment fail and gradually lead to Udara. Surgical tradition of Ayurveda identifies Tridoshaja Udara as Dooshyodara. All these descriptions clearly suggest that these Visha elements are capable of producing pathogenesis independent of the Doshas by direct vitiation of the Dhatus.
| Conclusion|| |
A clinical study of this type had never been done before and no other references than ancient classical texts were available at the start or at the end and though no new cases were taken after 11 years, routine follow-up was continued since pediatric cases have a long-life expectancy and many cases turned up in adults as well. Historical experiences on leukemia from all over the world, epidemiological studies support the strategical findings of Vishas as a strong possibility. The present environment, characterized by severe changes due to chemical invasions, as well as the etiology factors, supports the position taken in this article. Ayurveda's Visha (or carcinogens) concept is supported by extensive epidemiological reports as a major possibility.
Suggestion for future work
Oncology requires an integrated approach using modern facilities to diagnose and track the progress of the treatment. Steps need to be taken to minimize the exposure to toxic chemical come from a variety of sources. Gradually adopting the natural forming system will be helpful to reduce the prevalence of leukemia and other types of cancers in the rural areas. Scientific researches are needed to develop Ayurveda drugs that can be helpful in leukemia. The integrated approach will be more effective with a dedicated institute in this field.
Author wishes to thank Dr. M. Krishna Bhargava, Ex-Director, Kidwai Memorial Institute of Oncology, Bangalore. Dr, N.Lalitha, Professor of Medical oncology, Dr. L. Appaji, Professor, Head, Paediatric Oncology and Dr. Madhumati Professor, Haemato-oncology from Kidwai memorial Institute of Oncology Bangalore.
Financial support and sponsorship
This study was financially supported by Kidwai Memorial institute of Oncology, Bangalore.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Biemar F, Foti M. Global progress against cancer-challenges and opportunities. Cancer Biol Med 2013;10:183-6.
Ma X, Yu H. Global burden of cancer. Yale J Biol Med 2006;79:85-94.
Chwistek M. Recent advances in understanding and managing cancer pain. F1000Res 2017;6:945.
Gu J, Taylor CR. Practicing pathology in the era of big data and personalized medicine. Appl Immunohistochem Mol Morphol 2014;22:1-9.
Singh RH. Exploring issues in the development of Ayurvedic research methodology. J Ayurveda Integr Med 2010;1:91-5.
] [Full text]
Acharya YT, editor. Charaka Samhita of Agnivesha, Sutra Sthana. Reprint edition., Ch. 11., Ver. 7. Varanasi: Chaukhamba Orientalia; 2007. p. 69.
Acharya YT, editor. Charaka Samhita of Agnivesha, Sutra Sthana. Reprint edition., Ch. 11., Ver. 21-22. Varanasi: Chaukhamba Orientalia; 2007. p. 71.
Wajed SA, Laird PW, DeMeester TR. DNA methylation: An alternative pathway to cancer. Ann Surg 2001;234:10-20.
Smith A, Roman E, Howell D, Jones R, Patmore R, Jack A, et al
. The Haematological Malignancy Research Network (HMRN): A new information strategy for population based epidemiology and health service research. Br J Haematol 2010;148:739-53.
Davis AS, Viera AJ, Mead MD. Leukemia: An overview for primary care. Am Fam Physician 2014;89:731-8.
Greim H, Kaden DA, Larson RA, Palermo CM, Rice JM, Ross D, et al
. The bone marrow niche, stem cells, and leukemia: Impact of drugs, chemicals, and the environment. Ann N Y Acad Sci 2014;1310:7-31.
Nagel G, Weber D, Fromm E, Erhardt S, Lübbert M, Fiedler W, et al
. Epidemiological, genetic, and clinical characterization by age of newly diagnosed acute myeloid leukemia based on an academic population-based registry study (AMLSG BiO). Ann Hematol 2017;96:1993-2003.
Terwilliger T, Abdul-Hay M. Acute lymphoblastic leukemia: A comprehensive review and 2017 update. Blood Cancer J 2017;7:e577.
O'Leary M, Krailo M, Anderson JR, Reaman GH; Children's Oncology Group. Progress in childhood cancer: 50 years of research collaboration, a report from the Children's Oncology Group. Semin Oncol 2008;35:484-93.
Acharya YT, editor. Charaka Samhita of Agnivesha, Chikitsa Sthana. Reprint edition., Ch. 16, Ver. 34-36. Varanasi: Chaukhamba Orientalia; 2007. p. 528.
Acharya YT, editor. Charaka Samhita of Agnivesha, Chikitsa Sthana. Reprint edition., Ch. 16, Ver. 37. Varanasi: Chaukhamba Orientalia; 2007. p. 528.
Acharya YT, editor. Charaka Samhita of Agnivesha, Chikitsa Sthana. Reprint edition., Ch. 16, Ver. 132-133. Varanasi: Chaukhamba Orientalia; 2007. p. 532.
Acharya YT, editor. Charaka Samhita of Agnivesha, Chikitsa Sthana. Reprint edition., Ch. 4, Ver. 5-8. Varanasi: Chaukhamba Orientalia; 2007. p. 428.
Acharya YT, editor. Charaka Samhita of Agnivesha, Chikitsa Sthana. Reprint edition., Ch. 4, Ver. 19-21. Varanasi: Chaukhamba Orientalia; 2007. p. 429.
Acharya YT, editor. Charaka Samhita of Agnivesha, Chikitsa Sthana. Reprint edition., Ch. 8, Ver. 39-47. Varanasi: Chaukhamba Orientalia; 2007. p. 461.
Samal J. Ayurvedic management of pulmonary tuberculosis: A systematic review. J Intercult Ethnopharmacol 2016;5:86-91.
Acharya YT, editor. Charaka Samhita of Agnivesha, Chikitsa Sthana. Reprint edition., Ch. 23, Ver. 14. Varanasi: Chaukhamba Orientalia; 2007. p. 571.
Acharya YT, editor. Charaka Samhita of Agnivesha, Chikitsa Sthana. Reprint edition., Ch. 23, Ver. 24-27. Varanasi: Chaukhamba Orientalia; 2007. p. 572.
Acharya YT, editor. Charaka Samhita of Agnivesha, Chikitsa Sthana. Reprint edition., Ch. 24, Ver. 31. Varanasi: Chaukhamba Orientalia; 2007. p. 584.
Brahmananda Tripathy, editor. Asthanga Hridaya of Vagbhata, Nirmala Hindi Commentary. Reprint ed., Uttara Sthana; Visha Pratishedha Adhyaya, Chapter-35., Ver. 8-10. Delhi: Chaukhamba Sanskrit Pratisthan; 2009. p. 1144.
Acharya YT, editor. Sushruta Samhita of Sushruta, Sutra Sthana. Reprint edition., Ch. 15, Ver. 19. Varanasi: Chaukhambha Surabharati Prakashana; 2008. p. 71.
Acharya YT, editor. Charaka Samhita of Agnivesha, Sutra Sthana. Reprint edition., Ch. 17, Ver. 73-75. Varanasi: Chaukhamba Orientalia; 2007. p. 103.
Paradakara Shastri HS. Asthanga Hridaya of Vagbhata, Uttarasthana. Reprint edition., Chapter 35., Ver. 48-53. Varanasi: Chaukhambha Sanskrit Sansthan; 2012. p. 905-6.
Pombo-de-Oliveira MS, Andrade FG, Brisson GD, Dos Santos Bueno FV, Cezar IS, Noronha EP. Acute myeloid leukaemia at an early age: Reviewing the interaction between pesticide exposure and KMT2A-rearrangement. Ecancermedicalscience 2017;11:782.
Polychronakis I, Dounias G, Makropoulos V, Riza E, Linos A. Work-related leukemia: A systematic review. J Occup Med Toxicol 2013;8:14.
Snyder R. Leukemia and benzene. Int J Environ Res Public Health 2012;9:2875-93.
Tchounwou PB, Yedjou CG, Patlolla AK, Sutton DJ. Heavy metal toxicity and the environment. Exp Suppl 2012;101:133-64.
Paradakara Shastri HS. Asthanga Hridaya of Vagbhata, Uttarasthana. Reprint edition., Chapter 35., Ver. 33-37. Varanasi: Chaukhambha Sanskrit Sansthan; 2012. p. 904-5.
Paradakara Shastri HS. Asthanga Hridaya of Vagbhata, Uttarasthana. Reprint edition., Chapter 35., Ver. 6. Varanasi: Chaukhambha Sanskrit Sansthan; 2012. p. 904-2.
Jallow MF, Awadh DG, Albaho MS, Devi VY, Thomas BM. Pesticide knowledge and safety practices among farm workers in Kuwait: Results of a survey. Int J Environ Res Public Health 2017;14:340.
Aktar MW, Sengupta D, Chowdhury A. Impact of pesticides use in agriculture: Their benefits and hazards. Interdiscip Toxicol 2009;2:1-12.
Bajwa U, Sandhu KS. Effect of handling and processing on pesticide residues in food – A review. J Food Sci Technol 2014;51:201-20.
Kataria A, Trasande L, Trachtman H. The effects of environmental chemicals on renal function. Nat Rev Nephrol 2015;11:610-25.
Singh N, Gupta VK, Kumar A, Sharma B. Synergistic effects of heavy metals and pesticides in living systems. Front Chem 2017;5:70.
Leonard SS, Harris GK, Shi X. Metal-induced oxidative stress and signal transduction. Free Radic Biol Med 2004;37:1921-42.
Chen F, Ding M, Castranova V, Shi X. Carcinogenic metals and NF-κB activation. Mol Cell Biochem 2001;222:159-71.
Datta S, Chattopadhyay A. Physiological concept of hapten-carrier adduct vis-a-vis Garavisha. Ayu 2017;38:3-6.
] [Full text]
Ambikadatta Shastry, editor. Sushruta Samhita of Sushruta, Ayurveda Tatva Sandipika Hindi Commentary. Reprint ed., Nidana Sthana; Udara Nidana Adhyaya, Ch. 7., Ver. 11-13. Varanasi: Chaukhamba Sanskrit Sansthan; 2014. p. 333.