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Biomedical subjects

K L Mukherjee

Publications and source records attributed to K L Mukherjee.

At least 19 recordsLinked to original sources

Description of breastfeeding practices among poorer sections in Calcutta Metropolitan Area and its impact on postpartum infecundity.

Descriptions of breastfeeding practices among residents in slum areas of Kolkata and the influence of breastfeeding on postpartum amenorrhoea is the focus of this study. Three out of four women initiate breastfeeding after one hour of birth and three out of five women squeeze the first milk from the breast before breastfeeding. Though the median duration of breastfeeding is long, the duration of exclusive breastfeeding is much shorter. Breastfeeding during the first six months has a significant negative influence on the rate of return to menses.

Amenorrhea↗

Human fetal adrenal transplant: a possible role in relieving intractable pain in advanced rheumatoid arthritis.

BACKGROUND: The art of transplant surgery has gone a long way in establishing itself as an important discipline in medicine with the support of molecular biology, immunology, biochemistry, etc., as the ultimate treatment for the restoration of function of a failing organ. With the progressive increase in the life expectancy of human beings, there is an increasing discrepancy in the demand and supply of organ grafts. A less efficient alternative could be synthetic or mechanical grafts. Nucleated cell therapy, that is, cellular transplant, is a promising new area of study with its proven efficacy in neuro-degenerative disorders, hematopoietic disorders, diabetes and trauma-induced tissue loss, to name a few. Human fetal cell/tissue with its intrinsic hypo-antigenic advantage (up to 20 weeks of study), could be an interesting area of cellular/tissue transplant. Our research group has earlier reported on the safe use of umbilical cord whole blood and the successful transplant of a human fetal lung, heart, pancreas, liver, thymus, in an artificially prepared vascular subcutaneous axillary fold in which there was no feature of hyper-acute, acute or chronic rejection of the graft in HLA- and sex-randomized adult recipients, without concomitant immunosuppressives or radiation of the host to potentiate the survival of the fetal graft (within 20 weeks of gestation) within the lowest observation period of one month. The present study was aimed at examining the role of developing fetal adrenal transplants for patients with rheumatoid arthritis and severe pain due to involvement of inflammatory and neuropathic components. MATERIALS AND METHOD: Ten cases were enrolled in the present study after thorough informed consent and approval by the ethical committee of the institute. The age of the patients varied from 50 to 76 years and the group was comprised of three males and seven females. The age of the adrenal grafts varied from 16 to 20 weeks and these were collected from mothers admitted for hysterotomy and ligation. These long-standing rheumatoid patients (suffering for five to 15 years), presented with at least four of the seven 1987 revised criteria of the American College of Rheumatology for diagnosis of rheumatoid arthritis. A 2.5 cm long and 2 cm deep tissue space was dissected and prepared in each transplant recipient at the axilla using diathermy and knife after infiltrating the site with one percent lignocaine solution. The tissue collected from the consenting mother undergoing hysterotomy and ligation was inserted into this site, and the site was closed with 00 atraumatic vicryl. All necessary pre- and postoperative surgical precautions were taken to prevent infections. Sequential total count and differential count of leucocytes were undertaken to analyze the impact of the transplant on the host. After one month, a part of the transplanted fetal tissue was recovered for histological staining to examine whether there was any graft versus host reaction. RESULTS AND ANALYSIS: All ten patients tolerated the transplant procedure well. There was no fever, intractable pain or any other specific serious side-effect which could justify the removal of the transplant before one month. There was no discharge from the incision site and the healing of the scar was by and large normal. There was no unusual leucocytosis, lymphocytosis and the retrieved graft tissue did not suggest transplant rejection. However, there was definite pain relief, reduction in swelling and improvement of mobility of varying degree in a majority of the patients which was perceivable from the 15th day onwards. There was also a sense of well being (in 80%) and a gain in weight of three pounds or more (in 70%) among the fetal transplant recipients. DISCUSSION AND CONCLUSION: To understand the underlying mechanism, in case of pregnancy immunotolerance, we are of the opinion that emphasis should be placed on the role of non-specific and non-cytopathic blocking antibodies produced during pregnancy. The hypo-antigenicity of the developing human fetal system may possibly contribute to the production of this blocking antibody during pregnancy, and thus may play a role in the lack of recognition by the host's HLA system. This behaviour of the developing human fetal tissue provides some advantages over adult tissue for fetal cell/tissue transplantation purposes. The relief of pain, inflammation and restoration of mobility may be due to the effect of the transplanted adrenal graft, with the medullary component contributing to endorphin-like substance liberation and the cortical component contributing to glucocorticoid synthesis.

Adrenal Glands↗

Can human fetal cortical brain tissue transplant (up to 20 weeks) sustain its metabolic and oxygen requirements in a heterotopic site outside the brain? A study of 12 volunteers with Parkinson's disease.

BACKGROUND: Neural and stem cell transplantation is emerging as a potential treatment for neurodegenerative diseases from Parkinson's to Huntington's disease. Stereotactic placement of dopaminergic neurons in the caudate-putamen (striatum), is being attempted in centers of excellence and has proved to be beneficial. Basic research using cell transplantation indicates that structural development mechanisms seen in immature brains, i.e., fetal brains, can also function in the adult brain. The adult brain consumes 15% of the resting cardiac output for its metabolic needs. While most human tissues can sustain an anaerobic assault for a few minutes up to 30 minutes, a sudden total lack of oxygen supply to the brain cells in an adult will render the person unconscious within five to ten seconds. Our team has been working on the problem of human fetal tissue response to antigenic assault for the last two decades. In the present series, 12 patients with prolonged histories of Parkinsonism, who were not responding to anti-Parkinsonian drugs, and could not afford costly stereotactic surgery or deep brain stimulation and other modalities of recent Parkinson's disease treatment, were enrolled in the study. MATERIALS AND METHOD: After obtaining proper informed consents from the patients or their guardians and from the multidisciplinary ethical committee, the patients, varying in age from 45 to 75 years and suffering for many years with Parkinsonism, were enrolled in the heterotopic brain tissue transplant programme. We followed standard antiseptic, aseptic and premedication protocols, after selecting a proposed site of transplantation of the brain in the axillary fold of the skin, under local infiltration anaesthesia. In an adjacent OR, a fetus was collected from a consenting patient undergoing hysterotomy and ligation (before 20 weeks), under general anaesthesia. Within a minute of hysterotomy, the fetal brain tissue was dissected, and under the guidance of the operative microscope, 1 g of fetal cortical brain tissue was dissected and weighed in an electronic machine. The tissue was collected from around 1 cm of the frontal opercula of the developing human fetal brain and grafted in the already dissected and prepared subcutaneous site in the axilla and the skin was closed. Hematological parameters (Hgb; total count, Tc; differential count, Dc; erythocyte sedimentation rate, ESR) were estimated sequentially up to one month. A small portion of the transplanted tissue was retrieved after one to two months, and a serial histological study was done along with a clinical assessment of the disease condition as per the specifications of the Unified Parkinson's Disease Rating Scale. The results were matched with the pre-transplant ratings of the individual cases. Presenting dyskinesia was also rated (0-4), on the basis of objective criteria assessment like walking, putting on a coat, lifting a cup to drink, etc. RESULTS AND ANALYSIS: Initially 30 patients suffering from advanced Parkinson's disease (PD) were approached after getting the necessary clearance from the institutional multidisciplinary ethical committee; however, we have been able to arrange transplantation in only 12 cases so far. These patients were evaluated at the pre- and one month post-transplant period by the Unified Parkinson's Disease Rating Scale (0-108) and the minimum score was 40 in the motor portion of the unified scale at the pre-transplant state. Evaluation of the patients after one month revealed mild improvement of the pre-transplant scoring (up to 33.3%) in 41.6% of the cases, and moderate improvement (up to 66.6%) in another 41.6% of the cases. While 16.8% of the cases did not show any improvement from the basal score, i.e., the pre-transplant score, there was a definite sense of well being and rise in weight (2-4 pounds) noted in each case and there was also a reduction of the L-Dopa dosage in 75% of the cases. There was also a 58.3% improvement in the bradykinesia scoring from the pre-transplant level. What is intriguing is the survival, growth and proliferation of the grafted fetal brain tissue in the HLA- and sex-randomized adult axilla without any immunosuppressive support. Not a single histological study of the fetal brain tissues after removal from the axilla showed any signs of graft vs. host or inflammatory reaction (Figures 1-9) but there were features of growth of the transplanted cortical brain tissue along with its different components like neurogenesis, gliogenesis, early neovascularisation and angiogenesis, etc. There was also no systemic leucocytosis or lymphocytosis. DISCUSSION AND CONCLUSION: Histological evidence at the transplanted tissue site suggests that fetal cortical brain tissue can sustain life in sex-randomized, HLA-randomized adult hosts, without the support of immuno-suppressive drugs and the tacit support of the blood-CSF and blood-brain barrier and other specific requirements of adult brain cells in the skull. Whether the clinical improvement in PD is transient or long lasting is presently under investigation along with basic questions like, is it due to transplanted fetal dopaminergic or non-dopaminergic neurons or is it the growth factors and the cytokine mediated hitherto unknown reactions causing the clinical improvement.

Aged↗

A unique experience with human pre-immune (12 weeks) and hypo-immune (16 weeks) fetal thymus transplant in a vascular subcutaneous axillary fold in patients with advanced cancer: a report of two cases.

BACKGROUND: The successful development of fetal cell/tissue transplantation in adults has resulted in the possibility of eventual therapeutic solutions with a variety of intractable diseases. Umbilical cord whole blood transplantation appears to be safe in the adult system. In severe forms of DiGeorge Syndrome, cultured thymus transplant can help in the reconstitution of the immune condition of the host. Successful fetal tissue transplant in adults has raised the hope of future effective gene transplant and its manipulation prospects to combat many diseases including hemopathies, inborn errors of metabolism, immunodeficiencies and even cancer and AIDS. MATERIALS AND METHOD: Two cases of advanced cancer were treated with fetal (pre-immune 12 weeks and hypo-immune 16 weeks) thymus transplants in subcutaneous vascular axillary folds, which were removed after one month. Thymuses were collected from consenting mothers undergoing hysterotomy and ligation. RESULTS AND ANALYSIS: Patient I was suffering from non-Hodgkins lymphoma (Ann Arbor Stage IV) and was receiving cyclophosphomide, doxorubicin, vincristine and prednisolone after a course of radiotherapy; she developed leucopenia (2.400/cmm), which improved after receiving a 16-week human fetal thymic graft. The leucopenia was eventually over-corrected and the leucocyte count reached 44,000/cmm within a month, which was reversed after the thymus was taken out. Histology of the excised thymic graft showed growth and proliferation without any graft vs. host (GVH) reaction. Patient 2 was suffering from breast duct carcinoma (T4, N2, M0,) with estrogen, progesterone, and epidermal growth factor negative status, and was treated with modified radical mastectomy and axillary clearance followed by chemotherapy with cyclophosphomide, methotrexate and 5-fluorouracil for six cycles. She also received a 12-week-old human fetal thymus at the contra-lateral axilla which was removed after one month. In this case the peripheral leucocyte count did not show appreciable variation as in the first case. However, histology of the excised thymic graft showed growth and proliferation with an appearance of Hassel's corpuscles. CONCLUSION: Pre-immune and hypo-immune human fetal thymic transplant is not rejected in patients suffering from advanced cancer within one month (observation period). Thymic lymphocyte shedding in the correction of leucopenia in the background of non-Hodgkin's lymphoma may have many therapeutic implications.

Adolescent↗

Perception and practice regarding pulse polio immunisation in an urban community of Calcutta.

A survey was conducted at an Integrated Child Development Services (ICDS) Scheme project in North Calcutta among 656 mothers having children less than 3 years of age to assess their perception and practice regarding pulse polio immunisation (PPI). It was revealed that 91.8% of under 3-year children received PPI on 9-12-1995 and 94.4% on 20-1-1996. Major reasons for not accepting the services on those two days included 'mothers unaware' (22%), 'child too small' (30.5%), etc. Major source of first information was television (TV)/radio (57.2%) followed by anganwadi workers (AWWs) (33.8%). However, majority of the mothers were finally motivated for PPI by AWWs (58.8%) followed by the role of TV/radio (34.1%). Although 70.7% mothers knew the name of the vaccine correctly, only 3.5% mothers could tell the exact purpose of its administration. Most mothers (73%) opined that 2 drops of oral polio vaccine (OPV) was administered to their children and only 14.6% hoped that such programmes will be conducted by the Government in future. The average waiting time of mothers at immunisation centres was found to be 7.2 minutes.

Age Factors↗

Glycogen content & structure & some enzymes of glycogen metabolism in human foetal organs.

The glycogen content, and its structure and the enzymes involved in glycogenolysis in human foetal organs were studied at different periods of gestation. Of all the tissues studied glycogen content was found to be the highest in cardiac muscle. Very little glycogen was present in the foetal liver at 9-12 wk of gestation, this increased progressively to nearly 2 per cent at 24 wk. Glycogen content of placenta was lower than that of skeletal muscle and liver. The level of glycogen in adipose tissue, placenta and cerebrum was not high enough to play any role in glucose homeostasis of the foetus. Human foetal liver and skeletal muscle glycogen showed the normal branched structure while the liver glycogen was found to be unusually stable. Glycogen phosphorylase activity in the foetal liver and muscle was found to be low, i.e., about a fifth and a fourth of adult liver and muscle activity respectively. The stability of foetal liver glycogen and phosphorolytic activity in the liver and muscle indicate negligible glycogenolysis during foetal development. Glucose-6-phosphatase activity in foetal liver was undetectable below 12 wk of gestation, the activity increasing progressively up to 24 wk.

Fetus↗

Protein synthesis in human foetal brain & liver.

Anthropometric measurements were carried out on 772 normal human foetuses in Medical Termination of Pregnancy Clinics in Calcutta. Foetal brain constituted 14 per cent of body weights from 9 to 24 wk of gestation. The protein content/g of the foetal livers increased during 9-24 wk of gestation whereas that of the brain decreased slightly during this period. The rate of incorporation of 14C-leucine into 16,000 x g supernatant fractions of human foetal liver increased with progress of gestation. In foetal cerebrum and midbrain, the incorporation rate increased from 13 to 20 wk of gestation and then decreased. 16,000 x g pellet fractions of human foetal liver showed an increase of leucine incorporation with progress of gestation. However, the rate of incorporation in the foetal cerebrum was nearly the same at different periods of gestation.

Brain↗

Cathepsin D and 2',3'-cyclic nucleotide 3'-phosphohydrolase in developing human foetal brain.

Three peaks of proteinases were observed with hemoglobin, bovine serum albumin and casein as substrates at the pH of 3.5, 6.5 and 8.5, in prenatal human cerebral cortex. Cathepsin D (EC 3.4.23.5) was the most prominent, with hemoglobin as the preferred substrate. The enzyme was partially purified by Concanavalin A - Sepharose affinity chromatography and the nature of the active site was assessed with proteinase inhibitors. Inhibitor studies showed that similar to pepstatin A, benzethonium chloride was also strongly inhibitory to the enzyme. The distribution of cathepsin D, a neuronal marker, and 2',3'-cyclic nucleotide 3'-phosphohydrolase (EC 3.1.4.37), a oligodendroglial marker in foetal brain regions with increasing gestation revealed that neurogenesis and gliogenesis occur concomitantly from earlier periods of gestation. Glial marker acquisition was particularly high in medulla and in spinal cord between 20 and 25 weeks of gestation.

Brain↗

Aldose metabolism in developing human fetal brain and liver.

Aldose reductase, sorbitol dehydrogenase, and glucose-6-phosphate dehydrogenase enzyme activities were studied in human foetal brain and liver at different periods of gestation. Aldose reductase activity in liver disappears after 16 weeks of gestation whereas sorbitol dehydrogenase keeps on increasing in liver as well as in brain. In utero, some glucose metabolism may be mediated through an active sorbitol pathway in human fetuses.

Aldehyde Reductase↗

Changes in free amino acid levels in developing human foetal brain regions.

The levels of free amino acids were determined in human foetal brain regions during prenatal development. Variation in the distribution of amino acids and their rate of change in five segments of the CNS at different stages of ontogeny was observed. Striking developmental changes were found in the levels of aspartic acid in medulla-pons and spinal cord, glycine in the spinal cord, gamma-aminobutyric acid in the cerebral cortex, glutamic acid in the cerebral cortex, midbrain, and spinal cord, and taurine in the medulla-pons and spinal cord. At a late gestational period, glutamic acid was found most abundantly over all the brain regions, whereas the level of taurine was highest at an early gestational stage but not in spinal cord.

Amino Acids↗