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Biomedical subjects

A M Samuel

Publications and source records attributed to A M Samuel.

At least 37 records · Page 2Linked to original sources
PubMed1997

Photodynamic effects induced by meso-tetrakis[4-(carboxymethyleneoxy)phenyl]porphyrin using rat hepatic microsomes as model membranes.

Porphyrins, in combination with light, offer an alternate approach to the treatment of cancer, in the form of photodynamic therapy (PDT). With a view to locate new porphyrins for use in PDT, we evaluated the ability of a novel water-soluble porphyrin, meso-tetrakis[4-(carboxymethyleneoxy)phenyl]porphyrin (T4CPP) to induce photodamage in membranes, using rat hepatic microsomes as a model system. Hepatic microsomes treated with T4CPP and exposed to visible light showed significant lipid peroxidation, as assessed by the formation of conjugated dienes, lipid hydroperoxides, and thiobarbituric acid-reactive substances. The peroxidation induced was both time- and concentration-dependent. T4CPP plus light also resulted in the destruction of the microsomal enzymes adenosine triphosphatase and glucose-6-phosphatase. Analysis of the products of peroxidation and selective inhibition by specific inhibitors showed that the oxidative damage induced was mainly due to singlet oxygen and partly due to hydroxyl radical. The porphyrin T4CPP was efficiently labeled with 99mTc. When this 99mTc-labeled porphyrin was injected into a mammary-tumor-bearing rat, it accumulated in the tumor. Our studies suggest that T4CPP, due to its potential to localize in tumors and to induce membrane damage as exemplified by alteration in rat liver microsomes, may have possible applications in this new modality of cancer treatment.

Animals↗
PubMed1996

Quantification of salivary gland function in thyroid cancer patients treated with radioiodine.

PURPOSE: Damage to salivary gland function following external irradiation has been documented. However, the extent of damage following radioiodine (131I) therapy for thyroid cancer has not been adequately studied. We evaluated salivary dysfunction in Ca-thyroid patients treated with therapeutic doses of 131I. METHODS AND MATERIALS: A simple acquisition and analysis protocol using 99mTcO4- (pertechnatate) and a gamma camera computer system was planned. The uptake of 99mTcO4- by the salivary glands at 10 min and percent of excretion of 99mTcO4- from the glands in response to a sialogogue (lemon juice) was studied in 33 patients treated with 1.369-38.702 GBq of 131I (Mean = 10.16 GBq, standard deviation = 7.659 GBq) in addition to 14 athyreotic controls. RESULTS: Significant damage to the salivary gland in terms of abnormal percent uptake or excretion was noted in 72.73% of the patients. Forty-eight percent of the patients treated with 131I showed asymmetrical involvement of the salivary complexes as opposed to none of the controls. Reduction in uptake of 99mTc4- or response to sialogogue was dose dependent, being more marked with higher radioiodine doses. Parotid glands were more affected than submandibular glands following 131I therapy. CONCLUSIONS: 131I therapy produces a significant effect on salivary gland function that is dose related and becomes evident over a period of several months after treatment.

Humans↗
PubMed1996

Metastasis to the liver in well-differentiated carcinoma of the thyroid.

Eleven patients (6 women; 5 men) of a series of 1,916 developed liver metastasis from differentiated thyroid cancer within 3 months to 202 months after the initial diagnosis. Liver metastasis generally appeared after the onset of metastases at other sites. The metastasis to the liver was clinically suspected in 8 patients whereas it was accidentally diagnosed on ultrasound examination of abdomen for a complaint of back pain in 1 patient, on a whole body diagnostic radioiodine scan in 1 case, and on radionuclide liver scan in 1 patient. Three patients had noniodide concentrating hepatic metastasis which were treated with chemotherapy but with poor response. The remaining 8 patients were treated with radioiodine. The survival rate was poor but could not be attributed to liver metastasis per se because of the extensive metastatic disease at other sites.

Adenocarcinoma, Follicular↗
PubMed1996

Screening for microalbuminuria by RIA in 131I-treated thyroid cancer patients.

Thyroid cancer patients are treated with up to 9.9 GBq of 131I to ablate remnant thyroid tissue and/or any functioning metastases that may be present. Radioiodine therapy is repeated as often as required. However, only a small fraction of the 131I is taken up by remnant thyroid and metastases, the remainder being eliminated by the kidneys, which are therefore subject to irradiation. External radiation therapy to the kidneys is known to lead to nephritis and albuminuria. The study included 113 patients treated with one to four doses of 131I (1.1-9.9 GBq each dose) and followed up 1 month to more than 8 years later. Spot samples of urine were collected and microalbuminuria measured by in-house radioimmunoassay. Twelve patients had elevated levels (normal range up to 34 micrograms ml-1), but their clinical history revealed such predisposing factors as diabetes and/or hypertension and proteinuria before therapy commenced. The remaining patients had normoalbuminuria. Grouping the patients based on the total dose of 131I administered resulted in a median microalbuminuria of 2.4-12.9 micrograms ml-1. Hence, this study showed that the dose of 131I normally used in treating thyroid cancer does not increase microalbuminuria to any significant extent.

Adolescent↗
PubMed1995

Polymerase chain reaction in the diagnosis of tuberculosis. Comparison of two target sequences for amplification.

Amplification of a 340 bp sequence of the 38 kDa protein gene of Mycobacterium tuberculosis by the polymerase chain reaction has been developed. The sensitivity of this PCR was shown to be 10 fg both by agarose gel electrophoresis and Southern blot hybridisation being equivalent to 2-3 organisms and highly specific to M. tuberculosis and excluding even M. tuberculosis H37Ra and Mycobacterium bovis BCG. Sputum samples from patients with pulmonary tuberculosis gave a positivity rate of 45%. PCR was also performed using pt8 and pt9 primers which amplified a 541 bp sequence of IS6110. 41% of the above samples gave positive amplification. Three samples that were positive for 38 kDa sequence were negative for IS6110.

Bacterial Proteins↗
PubMed1995

Study of anti-idiotype antibodies to the monoclonal antibody HGT3a and its relation to the 38 kDa antigen of Mycobacterium tuberculosis.

The hypervariable regions of the immunoglobulins which function as the antigen binding sites are capable of provoking an antibody response and are referred to as anti-idiotypic antibodies. Antisera were raised in rabbits against the idiotypes of a mouse monoclonal antibody HGT3a which binds only to the 38 kDa antigen of the M. tuberculosis complex group of organisms. Idiotype specificity in these antisera was determined by dot ELISA, Western blot and solid phase inhibition assays. In vivo administration of this rabbit anti-idiotypic antibody to Swiss mice evoked an anti-anti-idiotypic antibody response, further confirming the internal antigen mimicry by the anti-idiotypic antibodies of the 38 kDa antigenic epitope and its potential use as a surrogate antigen. Antibody response to the anti-idiotypic antibodies in the sera of patients with pulmonary tuberculosis showed significant correlation with the antibody response to the 38 kDa antigen studied in the same clinical samples indicating a close similarity of the 38 kDa antigen of M. tuberculosis and the rabbit anti-idiotypic antibody produced against MoAb HGT3a.

Animals↗
PubMed1995

Differential kinetics of parotid and submandibular gland function as demonstrated by scintigraphic means and its possible implications.

Is the differential kinetics of secretion of saliva between the parotid and submandibular glands responsible for the relative difference in radiosensitivity? Radiation-induced dysfunction is more often noted in the parotid glands than the submandibular glands. This difference in susceptibility is often attributed to the difference in the cellular composition of these glands. During our studies using 99Tcm-pertechnetate to quantitate salivary gland function in patients treated with radioiodine, we noted frequent unstimulated discharge of saliva from the submandibular glands compared with parotid secretion. We hypothesize that the relative resistance of the submandibular glands could be due to the differential kinetics of the parotid and submandibular glands, as evidenced by using 99Tcm-pertechnetate to study their function.

Humans↗
PubMed1995

Evaluation of 99Tcm-labelled human immunoglobulin in animal models of experimentally induced inflammatory lesions.

Human immunoglobulin (HIG) was labelled with 99Tcm using different Sn-ligand (methylene diphosphonate, MDP) in high yields. The effect of Sn:ligand ratios and protein (HIG) on the biodistribution pattern of 99Tcm-HIG in an animal model of turpentine-induced inflammatory lesions was studied. 99Tcm-HIG was excreted predominantly via the renal pathway. The use of higher amounts of MDP and HIG resulted in relatively slower blood clearance and increased uptake of 99Tcm-HIG in various organs. Also, higher amounts of ligand [Sn:MDP (1:5)] resulted in significantly greater bone uptake (P < 0.001), while protein caused slower blood clearance and greater liver uptake. Despite the increased uptake of tracer in various organs, the ratio of inflamed:normal muscle uptake did not change significantly. A scintigraphic study was carried out with both 99Tcm-HIG and 99Tcm labelled with human serum albumin (HSA) in turpentine-induced inflammatory lesions produced in rabbits. The study revealed no significant differences in uptake early on, but the target:non-target ratio was higher with 99Tcm-HIG at 24 h. 99Tcm-HIG also had superior characteristics compared with 99Tcm-HSA.

Animals↗
PubMed1995

Effect of radioiodine therapy on pulmonary alveolar-capillary membrane integrity.

UNLABELLED: The effects of large doses of radioiodine on the pulmonary alveolar-capillary membrane using 99mTc-DTPA clearance as an index of pulmonary damage in subjects with pulmonary metastases of differentiated thyroid carcinoma were studied. METHODS: Technetium-99m-DTPA radioaerosols were generated by a dry aerosol generator. Data were acquired and analyzed for clearance half-time from the lungs with a scintillation camera. The study was carried out on 35 thyroid cancer patients with pulmonary metastases and on 32 patients without metastases; the results were compared to those of a control group comprising 52 subjects. The radiation dose delivered to the lungs from the therapeutic dose was calculated using MIRD methodology. RESULTS: Cumulative radioiodine doses varied from 5.9 to 44.2 GBq (158-1194 mCi). The half-time clearance of 99mTc-DTPA was comparable in both patient groups and was not related to the total administered radioiodine dosage or to the radiation dose delivered to the lungs. No changes were observed for periods up to 5 yr after receiving the last radioiodine dosage. Seven patients followed at regular intervals from 6 mo to 2 yr did not show abnormal 99mTc-DTPA clearance values. One patient did show low 99mTc-DTPA clearance half-time values, which were symptomatic radiation pneumonitis. She had received a total dose of 34 GBq (922 mCi) over a 4-yr period. CONCLUSION: The incidence of pulmonary damage resulting from radioiodine therapy for lung metastases of differentiated thyroid cancer is negligible, as evidenced by the normal pulmonary clearance half-time of 99mTc-DTPA aerosols.

Adult↗
PubMed1994

Detection of antibodies to defined M. tuberculosis antigen (38 kDa) in cerebrospinal fluids of patients with tuberculous meningitis.

Antibodies to the 38 kDa antigen of M. tuberculosis which is serospecific to the tuberculosis complex group of organisms was studied in CSF samples of patients with tuberculosis meningitis. Patients were classified into four groups, viz. post-mortem-proved, culture-proved, clinically suspected and tuberculoma. Anti-38 kDa antibody was detected by ELISA and was positive in 60%, 80% 62.5% and 0%, respectively in the four groups. Controls showed a false-positive detection of 5%. Follow-up of patients was done up to 6 weeks and antibody levels dropped in all the patient groups.

Antibodies, Bacterial↗
PubMed1994

Thyroid hormones in differentiated thyroid cancer.

In a study of 136 differentiated thyroid cancer patients referred for radioiodine therapy since January 1991, it was observed that 80 patients had metastatic disease. Of them, 51 had elevated levels of thyroglobulin (Tg), and of these 51 there were 15 patients who had functioning metastases with evidence of thyroid hormone synthesis by these metastases. All but 1 of these 15 cases with normal hormone levels in the circulation were follicular carcinomas with skeletal metastases. The response of these patients to radioiodine was poor. The group of patients with high Tg levels but low hormone synthesis and low circulating hormones responded better to radioiodine. Patients with low Tg levels and low hormone synthesis showed good response to radioiodine--especially patients with residual thyroid tissue after surgery and those with nodal disease.

Adenocarcinoma, Follicular↗
PubMed1994

Use of the recombinant 38-kDa antigen of Mycobacterium tuberculosis as an immunogen for specific antisera production.

The Mycobacterium tuberculosis 38-kDa protein antigen is one of the secreted immunodominant antigens showing high immunogenicity at B-cell and T-cell levels. Although monoclonal antibodies to this antigen have been produced, specific polyclonal antisera is required for standardization of specific immunodiagnostic assays. This protein has been overexpressed and purified from recombinant Escherichia coli using an inducible vector system. During each stage of expression and purification, the recombinant protein was used to immunize mice and rabbits by several methods: 1) as overexpressed protein present as inclusion bodies in recombinant E. coli; 2) embedded in a polyacrylamide gel; 3) fixed to a solid-phase nitrocellulose membrane and 4) emulsified with an adjuvant. All strategies yielded specific antisera as determined by enzyme-linked immunosorbent assay (ELISA) and immunoblot analyses. The results obtained, both quantitative (ELISA) and qualitative (immunoblot) demonstrate that the purified recombinant antigen retains its antigenicity and immunogenicity throughout the various steps in the process of expression and purification and serves as a potent antigen for production of specific antisera to be used in immunoassays.

Animals↗
PubMed1994

131I-MIBG scintigraphy in neural crest tumours.

Radioiodinated meta-iodobenzylguanidine (131I-MIBG) has been widely used for the diagnosis of neuroblastomas, pheochromocytomas, paragangliomas and medullary carcinomas of thyroid. We have developed a procedure for preparation of 131I-MIBG and studied its utility in diagnosis of primary and metastatic neural crest tumours. Studies were carried out in 54 patients. Of them 39 cases were of neuroblastomas, 1 pheochromocytoma; 6 operated medullary carcinomas; 5 paragangliomas; 2 Ewing's sarcoma and 1 Rhabdomyosarcoma; The sensitivity for the detection of primary tumours of neuroblastomas was 94% and for the detection of metastasis was 83%; while in the case of paragangliomas and medullary carcinoma, the sensitivity was 75% and 70% respectively. Our experience in the present study shows that 131I-MIBG scintigraphy is a sensitive and specific diagnostic tool to localise primary and metastatic disease of neural crest tumours.

3-Iodobenzylguanidine↗
PubMed1994

Radioiodine therapy for well-differentiated thyroid cancer: a quantitative dosimetric evaluation for remnant thyroid ablation after surgery.

UNLABELLED: The influence of cumulative absorbed dose, initial dose rate and mass of the remnant thyroid tissue on outcome of radioiodine treatment was assessed to determine an optimum value of absorbed dose and initial dose rate predictive of successful ablation. METHODS: In 87 patients with thyroid carcinoma treated with 0.85-9.55 GBq (23-258 mCi) of 131I to ablate residual thyroid tissue, the cumulative absorbed dose and the initial dose rate were calculated. Following therapy, the parameters of radioactive iodine uptake and effective half-life were determined in each patient from the surface neck exposure rates measured using a beta/gamma exposure rate meter. Mass of the thyroid remnant was determined from rectilinear images after scatter correction obtained from phantom studies. RESULTS: Sixty-eight patients showed complete ablation and 19 showed partial ablation of the thyroid remnant after radioiodine therapy. The cumulative absorbed doses delivered to the tissue in completely ablated and partially ablated groups were not significantly different (0.6 > p > 0.5). The initial dose rate delivered to the tissue in both groups, however, showed a significant difference (0.05 > p > 0.02). An initial dose rate of 3 Gy/hr or more completely ablated up to 5 g of tissue in 54 out of 62 patients (87.1%). Dose rate above 3 Gy/hr and cumulative doses above 300 Gy resulted in ablation in 50% of patients with more than 5 g of tissue. CONCLUSION: In patients receiving 131I to ablate thyroid remnant, the initial dose rate and the tissue mass are determinants of successful treatment response.

Combined Modality Therapy↗
PubMed1993

Serum ferritin in thyroid cancer.

Serum ferritin, one of the nonspecific tumor markers, was studied in 102 thyroid cancer patients, who had been thyroidectomized and were off thyroxine for 1 month, making them hypothyroid. Serum ferritin in thyroid cancer patients was not significantly different as compared to controls. Nevertheless, high levels of serum ferritin were observed in the thyroid cancer group as compared to primary hypothyroid patients. Furthermore, there was a significant difference in serum ferritin between thyroid cancer patients without metastasis and those with metastasis, patients with metastasis showing higher levels. Classification of thyroid cancer patients into different histological types revealed higher ferritin levels in follicular carcinoma as compared to papillary carcinoma. These data suggest that, although serum ferritin may not be a tumor marker for thyroid cancer, this parameter seems to be sensitive to the presence of metastasis and the histologic diagnosis.

Adenocarcinoma, Follicular↗
PubMed1993

Potassium iodate and its comparison to potassium iodide as a blocker of 131I uptake by the thyroid in rats.

Potassium iodide is the preferred thyroid blocker for personnel handling radioiodine and is recommended as a prophylaxis for the population in the near-field of a nuclear reactor which would be likely to be exposed to radioiodine in an accidental breach of containment. However, in hot and humid climates, this hygroscopic chemical has a poor shelf life due to hydrolytic loss of iodine vapors. On the other hand, another iodine-rich salt, potassium iodate (KIO3), is quite stable and has a much longer shelf life. The present study compares potassium iodide and KIO3 as thyroid blockers and examines the appropriate time at which they should be administered in case of radioiodine exposure. Either of the two were given in recommended dosage (100 mg stable iodine per 70 kg body weight) at -2, 0, +2, +4, +6, and +8 h after administration of tracer quantities of radioiodine (131I) to age-, weight-, and sex-matched rats. 131I uptake in thyroid was measured 24 h after its administration in the experimental animals and compared with placebo administered controls. Results suggest that KIO3 is as effective a thyroid blocking agent as potassium iodide. In comparison to controls, 24-h thyroid uptake of 131I can be substantially reduced if potassium iodide or KIO3 is given to the animals within 2-4 h after exposure to 131I. Another noteworthy observation is that KIO3 is effective even at 8 h when administered at twice the usual dosage in comparison to the single dose, which does not show appreciable thyroid blocking properties after 8 h.

Animals↗
PubMed1993

Measurement of serum thyrotropin levels using sensitive immunoradiometricassays in patients with chronic renal failure: alterations suggesting an intact pituitary thyroid axis.

Serum thyroid stimulating hormone (TSH) levels were measured in 127 patients with varying grade of chronic renal failure (CRF). Sensitive immunoradiometricassays (IRMA) were used so that small changes in TSH levels if any, could be appreciated, and to see if such alterations exhibit some relationship with those in thyroid hormone levels. Mean serum TSH levels in the patient group of 2.33 microU/ml (0.07-7.3) was significantly higher in comparison to 1.73 microU/ml (0.25-4.6) in normal subjects (p < 0.001). However, they were not significantly different when measured by radioimmunoassay (RIA) as compared to normals. Serum triiodothyronine (T3), thyroxine (T4) and free triiodothyronine (FT3) levels of 72 +/- 32 ng/dl, 7.4 +/- 2.6 micrograms/dl and 2.9 +/- 0.9 pg/ml were significantly lower than in normal subjects, whereas serum free thyroxine (FT4) showed a slight though not significant elevation. When patients were divided in three subgroups according to the degree of renal insufficiency, TSH levels showed a gradual rise with corresponding depression in their T3, FT3 and T4 levels. In 19 patients who were on hemodialysis (HD) and subsequently received successful renal transplantation, most of the thyroid function parameters returned towards the normals with TSH undergoing significant depression from their pretransplant levels as well as from normal levels. The results indicated that a slight but significant elevation in TSH levels could be revealed by sensitive IRMA in patients with CRF. Rising TSH levels with increasing renal insufficiency and its inverse relationship with T3 and T4 levels suggest maintenance of pituitary thyroid axis.(ABSTRACT TRUNCATED AT 250 WORDS)

Combined Modality Therapy↗